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Zhang S, Cao Y, Huang Y, Zhang X, Mou C, Qin T, Chen Z, Bao W. Abortive PDCoV infection triggers Wnt/β-catenin pathway activation, enhancing intestinal stem cell self-renewal and promoting chicken resistance. J Virol 2025; 99:e0013725. [PMID: 40135895 PMCID: PMC11998530 DOI: 10.1128/jvi.00137-25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Accepted: 02/28/2025] [Indexed: 03/27/2025] Open
Abstract
Porcine deltacoronavirus (PDCoV) is an emerging coronavirus causing economic losses to swine industries worldwide. PDCoV can infect chickens under laboratory conditions, usually with no symptoms or mild symptoms, and may cause outbreaks in backyard poultry and wildfowl, posing a potential risk of significant economic loss to the commercial poultry industry. However, the reasons for such a subdued reaction after infection are not known. Here, using chicken intestinal organoid monolayers, we found that although PDCoV infects them nearly as well as porcine intestinal organoid monolayers, infection did not result in detectable amounts of progeny virus. In ex vivo and in vivo experiments using chickens, PDCoV infection failed to initiate interferon and inflammatory responses. Additionally, infection did not result in a disrupted intestinal barrier nor a reduced number of goblet cells and mucus secretion, as in pigs. In fact, the number of goblet cells increased as did the secreted mucus, thereby providing an enhanced protective barrier. Ex vivo PDCoV infection in chicken triggered activation of the Wnt/β-catenin pathway with the upregulation of Wnt/β-catenin pathway genes (Wnt3a, Lrp5, β-catenin, and TCF4) and Wnt target genes (Lgr5, cyclin D1, and C-myc). This activation stimulates the self-renewal of intestinal stem cells (ISCs), accelerating ISC-mediated epithelial regeneration by significant up-regulation of PCNA (transiently amplifying cells), BMI1 (ISCs), and Lyz (Paneth cells). Our data demonstrate that abortive infection of PDCoV in chicken cells activates the Wnt/β-catenin pathway, which facilitates the self-renewal and proliferation of ISCs, contributing to chickens' resistance to PDCoV infection.IMPORTANCEThe intestinal epithelium is the main target of PDCoV infection and serves as a physical barrier against pathogens. Additionally, ISCs are charged with tissue repair after injury, and promoting rapid self-renewal of intestinal epithelium will help to re-establish the physical barrier and maintain intestinal health. We found that PDCoV infection in chicken intestinal organoid monolayers resulted in abortive infection and failed to produce infectious virions, disrupt the intestinal barrier, reduce the number of goblet cells and mucus secretion, and induce innate immunity, but rather increased goblet cell numbers and mucus secretion. Abortive PDCoV infection activated the Wnt/β-catenin pathway, enhancing ISC renewal and accelerating the renewal and replenishment of shed PDCoV-infected intestinal epithelial cells, thereby enhancing chicken resistance to PDCoV infection. This study provides novel insights into the mechanisms underlying the mild or asymptomatic response to PDCoV infection in chickens, which is critical for understanding the virus's potential risks to the poultry industry.
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Affiliation(s)
- Shuai Zhang
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Yanan Cao
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Yanjie Huang
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Xueli Zhang
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Chunxiao Mou
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China
| | - Tao Qin
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China
| | - Zhenhai Chen
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China
| | - Wenbin Bao
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
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Algaissi A, Khan E, Tabassum H, Samreen S, Khamjan NA, Lohani M, Khan S, Kameli N, Madkhali F, Ahmad IZ. Campesterol and dithymoquinone as a potent inhibitors of SARS cov-2 main proteases-promising drug candidates for targeting its novel variants. J Biomol Struct Dyn 2025; 43:2534-2548. [PMID: 38288958 DOI: 10.1080/07391102.2023.2301684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 09/13/2023] [Indexed: 02/16/2024]
Abstract
The sudden outbreak of the COVID-19 pandemic has currently taken approximately 2.4 million lives, with no specific medication and fast-tracked tested vaccines for prevention. These vaccines have their own adverse effects, which have severely affected the global healthcare system. The discovery of the main protease structure of coronavirus (Mpro/Clpro) has resulted in the identification of compounds having antiviral potential, especially from the herbal system. In this study, the computer-associated drug design tools were utilised to analyze the reported phytoconstituents of Nigella sativa for their antiviral activity against the main protease. Fifty-eight compounds were subjected to pharmacological parameter analysis to determine their lead likeness in comparison to the standard drugs (chloroquine and nirmatrelvir) used in the treatment of SARS-CoV-2. Nearly 31 compounds were docked against five different SARS-CoV-2 main proteases, and all compounds showed better binding affinity and inhibition constant against the proteases. However, dithymoquinone and campesterol displayed the best binding scores and hence were further subjected to dynamics and MMPBSA study for 100 ns. The stability analysis shows that dithymoquinone and campesterol show less variation in fluctuation in residues compared to standard complexes. Moreover, dithymoquinone exhibited higher binding affinity and favorable interaction followed by campesterol as compared to the standard drug. The in silico computational analysis provides a promising hit for regulating the main proteases activity.
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Affiliation(s)
- Abdullah Algaissi
- Department of Medical Laboratories Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
- Emerging and Epidemic Infectious Diseases Research Unit, Medical Research Center, Jazan University, Jazan, Saudi Arabia
| | - Elhan Khan
- Natural Products Laboratory, Department of Bioengineering, Integral University, Lucknow, Uttar Pradesh, India
| | - Heena Tabassum
- Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India
| | - Sadiyah Samreen
- Natural Products Laboratory, Department of Bioengineering, Integral University, Lucknow, Uttar Pradesh, India
| | - Nizar A Khamjan
- Department of Medical Laboratories Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Mohtashim Lohani
- Medical Research Centre, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Saif Khan
- Department of Basic Dental and Medical Sciences, College of Dentistry, Ha'il University, Ha'il, Saudi Arabia
| | - Nader Kameli
- Department of Medical Laboratories Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Faisal Madkhali
- Department of Medical Laboratories Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Iffat Zareen Ahmad
- Natural Products Laboratory, Department of Bioengineering, Integral University, Lucknow, Uttar Pradesh, India
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Algaissi A, Taha MME, Alamer E, Kameli N, Alhazmi A, Khamjan N, Abdelwahab SI. Trends and gaps in hydroxychloroquine and COVID-19 research (2020-2023): Performance and conceptual mapping. J Infect Public Health 2025; 18:102623. [PMID: 39813964 DOI: 10.1016/j.jiph.2024.102623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 10/17/2024] [Accepted: 12/12/2024] [Indexed: 01/18/2025] Open
Abstract
BACKGROUND Hydroxychloroquine and Chloroquine (CQ) and Hydroxychloroquine (HCQ) are antimalarial drugs with well-known anti-inflammatory and antiviral effects used to treat various diseases, with few side effects. After COVID-19 emergence, numerous researches from around the world have examined the potential of using CQ or HCQ as potential treatment of COVID-19. However, conflicting outcomes have been found in COVID-19 clinical trials after treatment with CQ or HCQ. This study aims to evaluate research on CQ and HCQ for COVID-19 treatment and prophylaxis control using bibliometric methods. METHODS We analyzed bibliometric data on HCQ and COVID-19 (HCQ-C19) quantitatively and semantically (2020-2023) using the Scopus database VOSviewer, Bibliometrix, and MS Excel. RESULTS Analyses of 7471 original and conference articles revealed that the total number of publications has continually increased. The country producing the most articles in this field was the United States, followed by Italy, India, and Spain. The top-productive authors on HCQ-C19 are Mussini, C., and Raoult, D. (Italy) with 23 and 21 articles, respectively. The top-impactful organization is IHU Méditerranée Infection, France. A Bibliometrix's network analysis based on the co-occurrence of keywords revealed the following themes HCQ-C19, including "clinical research/practice," "COVID-19," "thrombosis," "HCQ," "epidemiology," and "infectious disease." CONCLUSION In conclusion, the analysis reveals a growing interest in HCQ-C19 research. Prominent contributions come from the United States, Italy, India, and Spain. Key themes include clinical research/practice, COVID-19, thrombosis, HCQ, epidemiology, and infectious disease. Future recommendations include conducting well-designed clinical trials and fostering collaborative interdisciplinary efforts.
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Affiliation(s)
- Abdullah Algaissi
- Emerging and Epidemic Infectious Diseases Research Unit, Health Research Center, Jazan University, Jazan 45142, Saudi Arabia; Department of Medical Laboratories Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | | | - Edrous Alamer
- Emerging and Epidemic Infectious Diseases Research Unit, Health Research Center, Jazan University, Jazan 45142, Saudi Arabia; Department of Medical Laboratories Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Nader Kameli
- Emerging and Epidemic Infectious Diseases Research Unit, Health Research Center, Jazan University, Jazan 45142, Saudi Arabia; Department of Medical Laboratories Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Abdulaziz Alhazmi
- Emerging and Epidemic Infectious Diseases Research Unit, Health Research Center, Jazan University, Jazan 45142, Saudi Arabia; Department of Basic Medical Sciences, Faculty of Medicine, Jazan University, Jazan, 45142, Saudi Arabia
| | - Nizar Khamjan
- Department of Medical Laboratories Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
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Traore AM, Toure MK, Coulibaly YI, Keita M, Diarra B, Sanafo S, Dabo G, Kodio M, Traore B, Diarra A, Dicko A, Traore HA, Faye O, Minta DK. Factors of progression to severity and death in COVID-19 patients at two health care sites in Bamako, Mali. BMC Infect Dis 2025; 25:77. [PMID: 39825241 PMCID: PMC11742798 DOI: 10.1186/s12879-025-10456-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 01/07/2025] [Indexed: 01/20/2025] Open
Abstract
OBJECTIVES To analyze the clinical and biological characteristics and to evaluate the risk factors associated with the mortality of patients with COVID-19 in Commune IV of the District of Bamako. METHODS The cohort consisted of COVID-19 patients managed from March 2020 to June 2022 at the Bamako Dermatology Hospital and the Pasteur Polyclinic in Commune IV in Bamako. The studied variables were sociodemographic, clinical, and biological. For the analysis of deaths, explanatory variables were grouped into sociodemographic factors, comorbidities and symptoms. Binomial logistic regression models were used to identify mortality associated risk factors. RESULTS Among the 1319 included patients, 38.4% were asymptomatic, 46% and 15.5% developed moderate or severe COVID-19 respectively. The predominant signs were cough (48.5%), respiratory difficulty (24.6%) and headache (19.7%). Male were more common (58.2%). High blood pressure (19.9%) and diabetes (10%) were the main comorbidities. D-dimers < 0.5 μg/l was found in 53.3% of cases and the mean hemoglobin level was 12.9 ± 1.7 g/l. The case fatality rate was 3.71% in our series. In bivariate analysis, age > 60 years, high blood pressure, diabetes, clinical severity, D-dimers < 0.5 μg/l were associated with death. Using binomial logistic regression method, age > 60 years, increased heart rate, disease severity level and mainly acute respiratory distress syndrome (polypnea, difficulty breathing) were the factors found associated with death. After adjusting for all the assessed factors, age < 60 years [aHR = 0.15 (0.06-0.35)] and administration of azithromycin [aHR = 0.31 (0.1-0.97)] were protective factors while higher respiratory rate [aHR = 1.14 (1.07-1.22)] and difficulty breathing [aHR = 3.06 (1.03-9.13)] were risk factors associated with death. CONCLUSION These main findings elucidate the factors associated with severity and lethality external of health care system constraints. Advanced age, higher heart rate and the development of respiratory distress were the factors significantly associated with increased fatalities.
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Affiliation(s)
- Abdoulaye Mamadou Traore
- Centre Hospitalier Universitaire du Point G (Point G University Hospital), Bamako, Mali.
- Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali.
| | - Mamadou Karim Toure
- Hopital de Dermatologie de Bamako (Bamako Dermatology Hospital), Bamako, Mali
- Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali
| | - Yaya Ibrahim Coulibaly
- Hopital de Dermatologie de Bamako (Bamako Dermatology Hospital), Bamako, Mali
- Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali
| | - Modibo Keita
- Hopital de Dermatologie de Bamako (Bamako Dermatology Hospital), Bamako, Mali
| | - Bakary Diarra
- Polyclinique Pasteur (Pasteur Polyclinic), Bamako, Mali
| | - Salif Sanafo
- Polyclinique Pasteur (Pasteur Polyclinic), Bamako, Mali
| | - Garan Dabo
- Hopital du Mali (Mali Hospital, Bamako, Mali
- Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali
| | - Mamoudou Kodio
- Hopital de Dermatologie de Bamako (Bamako Dermatology Hospital), Bamako, Mali
- Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali
| | - Bourama Traore
- Hopital de Dermatologie de Bamako (Bamako Dermatology Hospital), Bamako, Mali
- Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali
| | - Aminata Diarra
- Hopital de Dermatologie de Bamako (Bamako Dermatology Hospital), Bamako, Mali
- Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali
| | - Adama Dicko
- Hopital de Dermatologie de Bamako (Bamako Dermatology Hospital), Bamako, Mali
- Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali
| | - Hamar A Traore
- Polyclinique Pasteur (Pasteur Polyclinic), Bamako, Mali
- Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali
| | - Ousmane Faye
- Hopital de Dermatologie de Bamako (Bamako Dermatology Hospital), Bamako, Mali
- Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali
| | - Daouda K Minta
- Centre Hospitalier Universitaire du Point G (Point G University Hospital), Bamako, Mali
- Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali
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5
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Latarissa IR, Khairinisa MA, Iftinan GN, Meiliana A, Sormin IP, Barliana MI, Lestari K. Efficacy and Safety of Antimalarial as Repurposing Drug for COVID-19 Following Retraction of Chloroquine and Hydroxychloroquine. Clin Pharmacol 2025; 17:1-11. [PMID: 39845335 PMCID: PMC11748038 DOI: 10.2147/cpaa.s493750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 01/06/2025] [Indexed: 01/24/2025] Open
Abstract
Various repurposing drugs have been tested for their efficacy on coronavirus disease 2019 (COVID-19), including antimalarial drugs. During the pandemic, Chloroquine (CQ) and Hydroxychloroquine (HCQ) demonstrated good potential against COVID-19, but further studies showed both drugs had side effects that were more dangerous than the efficacy. This made World Health Organization (WHO) ban the usage for COVID-19 patients. In this context, there is a need to explore other antimalarial drugs as potential therapies for COVID-19. This study provides a descriptive synthesis of clinical trials evaluating antimalarial drugs for COVID-19 treatment conducted after the withdrawal of CQ and HCQ. The method was a literature study using the keywords "antimalarial", "COVID-19", "SARS-CoV-2", "clinical trial", and "randomized controlled trial" on the MEDLINE, Scopus, and Cochrane databases. Inclusion criteria were published clinical trials with randomized controlled trials (RCTs) on the efficacy and safety of single antimalarial drugs for COVID-19, published in English and excluding combination therapies. The results showed 3 antimalarial drugs, namely Quinine Sulfate (QS), Atovaquone (AQ), and Artemisinin-Piperaquine (AP), had gone through clinical trial to assess efficacy and safety against COVID-19 patients. Out of the 3 drugs, only AP showed significant results in the primary outcome, which was the time required to reach undetectable levels of SARS-CoV-2. Furthermore, the intervention group took 10.6 days, and the control group took 19.3 days (p=0.001). Based on this review, AP showed significant potential as a therapy in the fight against COVID-19.
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Affiliation(s)
- Irma Rahayu Latarissa
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia
- Medication Therapy Adherence Clinic (MTAC), Universitas Padjadjaran, Sumedang, Indonesia
| | - Miski Aghnia Khairinisa
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia
| | - Ghina Nadhifah Iftinan
- Medication Therapy Adherence Clinic (MTAC), Universitas Padjadjaran, Sumedang, Indonesia
| | - Anna Meiliana
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia
- Prodia Clinical Laboratory, Central Jakarta, Indonesia
| | - Ida Paulina Sormin
- Faculty of Pharmacy, University of 17 August 1945 Jakarta, Jakarta, Indonesia
- Prodia Diacro Laboratory, Jakarta, Indonesia
| | - Melisa Intan Barliana
- Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia
- Center of Excellence for Pharmaceutical Care Innovation, Universitas Padjadjaran, Sumedang, Indonesia
| | - Keri Lestari
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia
- Medication Therapy Adherence Clinic (MTAC), Universitas Padjadjaran, Sumedang, Indonesia
- Center of Excellence for Pharmaceutical Care Innovation, Universitas Padjadjaran, Sumedang, Indonesia
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Mishra R, da Cunha Xavier J, Kumar N, Krishna G, Dhakad PK, Dos Santos HS, Bandeira PN, Rodrigues THS, Gondim DR, Ribeiro WHF, da Silva DS, Teixeira AMR, Pereira WF, Marinho ES, Sucheta. Exploring Quinoline Derivatives: Their Antimalarial Efficacy and Structural Features. Med Chem 2025; 21:96-121. [PMID: 40007183 DOI: 10.2174/0115734064318361240827072124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 06/14/2024] [Accepted: 06/26/2024] [Indexed: 02/27/2025]
Abstract
OBJECTIVES Malaria continues to be the primary cause of mortality worldwide, and timely recognition and prompt intervention are crucial in mitigating adverse consequences. This review article aims to examine the effectiveness and structural characteristics of quinoline-based compounds as antimalarial agents. It specifically focuses on their therapeutic effects as well as potential prospects for exploring structure-activity relationship (SAR). In addition, this study aims to identify lead compounds that can efficiently battle multidrug-resistant forms of Plasmodium falciparum and Plasmodium vivax. METHODS A comprehensive review was conducted to evaluate the effectiveness of quinoline-based antimalarial medications in eradicating P. falciparum and P. vivax. The mechanism of action and SAR of these compounds were analyzed. RESULTS Quinoline-based antimalarials demonstrated significant effectiveness in eliminating P. falciparum parasites, particularly in regions severely impacted by malaria, including Africa and Asia. These compounds were found to exhibit tolerance and immune-modulating properties, indicating their potential for more widespread utilization. The investigation identified various new quinoline compounds with improved antimalarial activity, including metal-chloroquine complexes, diaminealkyne chloroquines, and cinnamoylated chloroquine hybrids. This study explored different mechanisms by which these compounds interact with parasites, including their ability to accumulate in the parasite's acidic food vacuoles and disrupt heme detoxification. The derivatives demonstrated strong efficacy against chloroquine-resistant strains and yielded positive results. CONCLUSION Quinoline-based compounds represent a promising avenue for combating malaria due to their demonstrated efficacy against P. falciparum and P. vivax parasites. Further research on their mechanisms of action and SAR could lead to the development of more effective antimalarial medications.
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Affiliation(s)
- Raghav Mishra
- Department of Pharmacy, Lloyd School of Pharmacy, Knowledge Park II, Greater Noida, Uttar Pradesh 201306, India
| | | | - Nitin Kumar
- Department of Pharmacy, Saraswathi College of Pharmacy, Anwarpur, Pilkhuwa, India
| | - Gaurav Krishna
- Department of Pharmacy, GLA University, Mathura, 281406, Uttar Pradesh, India
| | - Prashant Kumar Dhakad
- Department of Pharmacy, Suresh Gyan Vihar University, Gyan vihar Marg Jagatpura Jaipur, 302017, Rajasthan, India
| | - Helcio Silva Dos Santos
- Department of Biological Chemistry, Regional University of Cariri, Crato-CE, Brazil
- Center for Exact Sciences and Technology - Chemistry Course, Vale do Acaraú University, Sobral, CE, Brazil
| | - Paulo Nogueira Bandeira
- Center for Exact Sciences and Technology - Chemistry Course, Vale do Acaraú University, Sobral, CE, Brazil
| | | | - Diego Romao Gondim
- Center for Exact Sciences and Technology - Chemistry Course, Vale do Acaraú University, Sobral, CE, Brazil
| | | | - Draulio Sales da Silva
- Center for Exact Sciences and Technology - Chemistry Course, Vale do Acaraú University, Sobral, CE, Brazil
| | | | | | - Emmanuel Silva Marinho
- Postgraduate Program in Natural Sciences, State University of Ceara, Fortaleza, CE, Brazil
| | - Sucheta
- School of Medical & Allied Sciences, K.R. Mangalam University, Sohna Road, Gurugram, India
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Parua P, Ghosh S, Jana K, Seth A, Debnath B, Rout SK, Sarangi MK, Dash R, Halder J, Rajwar TK, Pradhan D, Rai VK, Dash P, Das C, Kar B, Ghosh G, Rath G. Therapeutic Potential of Neutralizing Monoclonal Antibodies (nMAbs) against SARS-CoV-2 Omicron Variant. Curr Pharm Des 2025; 31:753-773. [PMID: 39543801 DOI: 10.2174/0113816128334441241108050528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Revised: 09/21/2024] [Accepted: 09/27/2024] [Indexed: 11/17/2024]
Abstract
BACKGROUND The COVID-19 pandemic has spurred significant endeavors to devise treatments to combat SARS-CoV-2. A limited array of small-molecule antiviral drugs, specifically monoclonal antibodies and interferon therapy, have been sanctioned to treat COVID-19. These treatments typically necessitate administration within ten days of symptom onset. There have been reported reductions in the effectiveness of these medications due to mutations in non-structural protein genes, particularly against Omicron subvariants. This underscores the pressing requirement for healthcare systems to continually monitor pathogen variability and its impact on the efficacy of prevention and treatments. AIM This review aimed to comprehend the therapeutic benefits and recent progress of nMAbs for preventing and treating the Omicron variant of SARS-CoV-2. RESULTS AND DISCUSSION Neutralizing monoclonal antibodies (nMAbs) provide a treatment avenue for severely affected individuals, especially those at high risk for whom vaccination is not viable. With their specific epitope affinity, they pose no significant risk of severe adverse effects. The degree of reduction in neutralization varies significantly across different monoclonal antibodies and variant combinations. For instance, Sotrovimab maintained its neutralization effectiveness against Omicron BA.1, but exhibited diminished efficacy against BA.2, BA.4, BA.5, and BA.2.12.1. CONCLUSION Bebtelovimab has been observed to preserve its efficacy against all subtypes of the Omicron variant. Subsequently, WKS13, mAb-39, 19n01, F61-d2 cocktail, etc., have become effective. This review has highlighted the therapeutic implications of nMAbs in SARS-CoV-2 Omicron treatment and the progress of COVID-19 drug discovery.
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Affiliation(s)
- Pijus Parua
- Department of Pharmaceutical Technology, Bharat Technology, Uluberia, Howrah, West Bengal-711316, India
| | - Somnath Ghosh
- Department of Pharmaceutical Technology, Bharat Technology, Uluberia, Howrah, West Bengal-711316, India
| | - Koushik Jana
- Department of Pharmaceutical Technology, Bharat Technology, Uluberia, Howrah, West Bengal-711316, India
| | - Arnab Seth
- Department of Pharmaceutical Technology, Bharat Technology, Uluberia, Howrah, West Bengal-711316, India
| | - Biplab Debnath
- Department of Pharmaceutical Technology, Bharat Technology, Uluberia, Howrah, West Bengal-711316, India
| | - Saroj Kumar Rout
- LNK International, Inc., Hauppauge, New York-11788, United States
| | - Manoj Kumar Sarangi
- Department of Pharmaceutics, Amity Institute of Pharmacy, Amity University, Lucknow-226024, Uttar Pradesh, India
| | - Rasmita Dash
- Department of Pharmaceutics, School of Pharmacy and Life Sciences, Centurion University of Technology and Management, Bhubaneswar-752050, Odisha, India
| | - Jitu Halder
- School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University), Kalinga Nagar, Bhubaneswar-751030, Odisha, India
| | - Tushar Kanti Rajwar
- School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University), Kalinga Nagar, Bhubaneswar-751030, Odisha, India
| | - Deepak Pradhan
- School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University), Kalinga Nagar, Bhubaneswar-751030, Odisha, India
| | - Vineet Kumar Rai
- School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University), Kalinga Nagar, Bhubaneswar-751030, Odisha, India
| | - Priyanka Dash
- School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University), Kalinga Nagar, Bhubaneswar-751030, Odisha, India
| | - Chandan Das
- School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University), Kalinga Nagar, Bhubaneswar-751030, Odisha, India
| | - Biswakanth Kar
- School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University), Kalinga Nagar, Bhubaneswar-751030, Odisha, India
| | - Goutam Ghosh
- School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University), Kalinga Nagar, Bhubaneswar-751030, Odisha, India
| | - Goutam Rath
- School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University), Kalinga Nagar, Bhubaneswar-751030, Odisha, India
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8
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Behzadi P, Chandran D, Chakraborty C, Bhattacharya M, Saikumar G, Dhama K, Chakraborty A, Mukherjee S, Sarshar M. The dual role of toll-like receptors in COVID-19: Balancing protective immunity and immunopathogenesis. Int J Biol Macromol 2025; 284:137836. [PMID: 39613064 DOI: 10.1016/j.ijbiomac.2024.137836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Revised: 11/01/2024] [Accepted: 11/17/2024] [Indexed: 12/01/2024]
Abstract
Toll-like receptors (TLRs) of human are considered as the most critical immunological mediators of inflammatory pathogenesis of COVID-19. These immunoregulatory glycoproteins are located on the surface and/or intracellular compartment act as innate immune sensors. Upon binding with distinct SARS-CoV-2 ligand(s), TLRs signal activation of different transcription factors that induce expression of the proinflammatory mediators that collectively induce 'cytokine storm'. Similarly, TLR activation is also pivotal in conferring protection to infection and invasion as well as upregulating the tissue repair pathways. This dual role of the human TLRs in deciding the fate of SARS-CoV-2 has made these receptor proteins as the critical mediators of immunoprotective and immunopathogenic consequences associated with COVID-19. Herein, pathbreaking discoveries exploring the immunobiological importance of the TLRs in COVID-19 and developing TLR-directed therapeutic intervention have been reviewed by accessing the up-to-date literatures available in the public domain/databases. In accordance with our knowledge in association with the importance of TLRs' role against viruses and identification of viral particles, they have been recognized as suitable candidates with high potential as vaccine adjuvants. In this regard, the agonists of TLR4 and TLR9 have effective potential in vaccine technology while the others need further investigations. This comprehensive review suggests that basal level expression of TLRs can act as friends to keep our body safe from strangers but act as a foe via overexpression. Therefore, selective inhibition of the overexpressed TLRs appears to be a solution to counteract the cytokine storm while TLR-agonists as vaccine adjuvants could lessen the risk of infection in the naïve population.
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Affiliation(s)
- Payam Behzadi
- Department of Microbiology, Shahr-e-Qods Branch, Islamic Azad University, Tehran, 37541-374, Iran.
| | | | - Chiranjib Chakraborty
- Department of Biotechnology, School of Life Science and Biotechnology, Adamas University, Kolkata, 700126, West Bengal, India
| | - Manojit Bhattacharya
- Department of Zoology, Fakir Mohan University, VyasaVihar, Balasore, 756020, Odisha, India
| | - Guttula Saikumar
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Bareilly, Izatnagar, Uttar Pradesh, 243122, India
| | - Kuldeep Dhama
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Bareilly, Izatnagar, Uttar Pradesh, 243122, India.
| | - Ankita Chakraborty
- Integrative Biochemistry & Immunology Laboratory, Department of Animal Science, Kazi Nazrul University, Asansol, 713340, West Bengal, India
| | - Suprabhat Mukherjee
- Integrative Biochemistry & Immunology Laboratory, Department of Animal Science, Kazi Nazrul University, Asansol, 713340, West Bengal, India.
| | - Meysam Sarshar
- Research Laboratories, Bambino Gesù Children's Hospital-IRCCS, 00146, Rome, Italy
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9
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Wang H, Yang Q, Mao Y, Ding H, Huang P, Zhan Z. The efficacy and safety of hydroxychloroquine at different doses and courses for COVID-19 prevention: a systematic review and network meta-analysis. Expert Rev Anti Infect Ther 2024; 22:1209-1220. [PMID: 39365687 DOI: 10.1080/14787210.2024.2413419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Revised: 09/30/2024] [Accepted: 10/03/2024] [Indexed: 10/06/2024]
Abstract
BACKGROUND The optimal strategy for using hydroxychloroquine to prevent coronavirus disease 2019 (COVID-19) in patients, either before or after exposure, remains unclear. We evaluated the safety and efficacy of different doses and treatment durations of hydroxychloroquine for COVID-19 prevention. METHOD Databases including PubMed, Web of Science, Cochrane Library, EMBASE, Medline, and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) comparing different doses of hydroxychloroquine for COVID-19 prevention, from their inception to February 2024. RESULTS A total of 20 RCTs involving 12,372 patients were included. Meta-analysis results showed no significant difference between the hydroxychloroquine and control groups in reducing the incidence of syndrome coronavirus type 2 (SARS-CoV-2) positivity (OR = 0.83, 95% CI = 0.67, 1.03). However, the subgroup receiving a daily dose of 200-400 mg (OR = 0.62, 95% CI = 0.51, 0.75) and a treatment duration of 5-8 weeks (OR = 0.52, 95% CI = 0.31, 0.88) showed statistically significant reductions in SARS-CoV-2 positivity. According to the surface under the cumulative ranking curve (SUCRA), the most effective intervention was a 200-400 mg dose for 5-8 weeks. . CONCLUSIONS A hydroxychloroquine dose of 200-400 mg for a duration of 5-8 weeks may moderately reduce the risk of COVID-19 with a relatively low risk of adverse events.
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Affiliation(s)
- Hang Wang
- Department of Pharmacy, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Pharmacy, National Regional Medical Center, Binhai Campus of The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Qiyuan Yang
- Department of Pharmacy, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Pharmacy, National Regional Medical Center, Binhai Campus of The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Yinjun Mao
- Department of Pharmacy, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Pharmacy, National Regional Medical Center, Binhai Campus of The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Haibo Ding
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Pinfang Huang
- Department of Pharmacy, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Pharmacy, National Regional Medical Center, Binhai Campus of The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Zhikun Zhan
- Department of Pharmacy, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Pharmacy, National Regional Medical Center, Binhai Campus of The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
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10
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Toro A, Arévalo AP, Pereira-Gómez M, Sabater A, Zizzi EA, Perbolianachis P, Pascual G, Lage-Vickers S, Pórfido JL, Achinelli I, Seniuk R, Bizzotto J, Sanchis P, Olivera A, Leyva A, Moreno P, Costábile A, Fajardo A, Carrión F, Fló M, Olivero-Deibe N, Rodriguez F, Nin N, Anselmino N, Labanca E, Vazquez E, Cotignola J, Alonso DF, Valacco MP, Marti M, Gentile F, Cherkasov A, Crispo M, Moratorio G, Gueron G. Blood matters: the hematological signatures of Coronavirus infection. Cell Death Dis 2024; 15:863. [PMID: 39609423 PMCID: PMC11605097 DOI: 10.1038/s41419-024-07247-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 11/08/2024] [Accepted: 11/13/2024] [Indexed: 11/30/2024]
Abstract
Recent developments have broadened our perception of SARS-CoV-2, indicating its capability to affect the body systemically beyond its initial recognition as a mere respiratory pathogen. However, the pathways of its widespread are not well understood. Employing a dual-modality approach, we integrated findings from a Murine Hepatitis Virus (MHV) infection model with corroborative clinical data to investigate the pervasive reach of Coronaviruses. The novel presence of viral particles within red blood cells (RBCs) was demonstrated via high-resolution transmission electron microscopy, with computational modeling elucidating a potential heme-mediated viral entry mechanism via Spike protein affinity. Our data affirm viral localization in RBCs, suggesting heme moieties as facilitators for cellular invasion. Exacerbation of MHV pathology upon hemin administration, contrasted with chloroquine-mediated amelioration, underscoring a heme-centric pathway in disease progression. These observations extend the paradigm of Coronavirus pathogenicity to include hemoprotein interactions. This study casts new light on the systemic invasion capabilities of Coronaviruses, linking RBC hemoproteins with viral virulence. The modulation of disease severity through heme-interacting agents heralds a promising avenue for COVID-19 therapeutics. Our findings propose a paradigm shift in the treatment approach, leveraging the virus-heme interplay as a strategic hinge for intervention.
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Affiliation(s)
- Ayelen Toro
- Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
- Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina.
| | - Ana P Arévalo
- Unidad de Biotecnología en Animales de Laboratorio, Institut Pasteur de Montevideo, Montevideo, Uruguay
| | - Marianoel Pereira-Gómez
- Laboratorio de Virología Molecular, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
- Laboratorio de Evolución Experimental de Virus, Institut Pasteur de Montevideo, Montevideo, Uruguay
| | - Agustina Sabater
- Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
- Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina
- Instituto de Tecnología (INTEC), Universidad Argentina de la Empresa (UADE), Buenos Aires, Argentina
| | - Eric A Zizzi
- PolitoBIOMed Lab, Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy
- Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON, Canada
| | - Paula Perbolianachis
- Laboratorio de Virología Molecular, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
- Laboratorio de Evolución Experimental de Virus, Institut Pasteur de Montevideo, Montevideo, Uruguay
| | - Gaston Pascual
- Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
- Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Sofia Lage-Vickers
- Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
- Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Jorge L Pórfido
- Unidad de Biotecnología en Animales de Laboratorio, Institut Pasteur de Montevideo, Montevideo, Uruguay
| | - Ines Achinelli
- Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
- Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Rocio Seniuk
- Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
- Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Juan Bizzotto
- Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
- Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina
- Instituto de Tecnología (INTEC), Universidad Argentina de la Empresa (UADE), Buenos Aires, Argentina
| | - Pablo Sanchis
- Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
- Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina
- Instituto de Tecnología (INTEC), Universidad Argentina de la Empresa (UADE), Buenos Aires, Argentina
| | - Alvaro Olivera
- Laboratorio de Alta Resolución, Departamento de Desarrollo Tecnológico, Centro Universitario Regional Este (CURE), Universidad de la República, Rocha, Uruguay
| | - Alejandro Leyva
- Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay
- Unidad de Bioquímica y Proteómica Analíticas, Institut Pasteur de Montevideo, Montevideo, Uruguay
| | - Pilar Moreno
- Laboratorio de Virología Molecular, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
- Laboratorio de Evolución Experimental de Virus, Institut Pasteur de Montevideo, Montevideo, Uruguay
| | - Alicia Costábile
- Laboratorio de Virología Molecular, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
- Laboratorio de Evolución Experimental de Virus, Institut Pasteur de Montevideo, Montevideo, Uruguay
- Centro de Innovación en Vigilancia Epidemiológica, Institut Pasteur de Montevideo, Montevideo, Uruguay
- Sección Bioquímica, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
| | - Alvaro Fajardo
- Laboratorio de Virología Molecular, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
- Laboratorio de Evolución Experimental de Virus, Institut Pasteur de Montevideo, Montevideo, Uruguay
| | - Federico Carrión
- Laboratorio de Inmunovirología, Institut Pasteur de Montevideo, Montevideo, Uruguay
| | - Martín Fló
- Laboratorio de Inmunovirología, Institut Pasteur de Montevideo, Montevideo, Uruguay
- Departamento de Inmunobiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
| | | | - Fernando Rodriguez
- Unidad de Cuidados Intensivos, Hospital Español "Juan José Crottoggini", Administración de Servicios de Salud del Estado, Montevideo, Uruguay
| | - Nicolas Nin
- Unidad de Cuidados Intensivos, Hospital Español "Juan José Crottoggini", Administración de Servicios de Salud del Estado, Montevideo, Uruguay
| | - Nicolas Anselmino
- Department of Genitourinary Medical Oncology and The David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Estefania Labanca
- Department of Genitourinary Medical Oncology and The David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Elba Vazquez
- Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
- Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Javier Cotignola
- Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
- Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Daniel F Alonso
- Centro de Oncología Molecular y Traslacional y Plataforma de Servicios Biotecnológicos, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Bernal, Argentina
| | - Maria P Valacco
- Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
- Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Marcelo Marti
- Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
- Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Francesco Gentile
- Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON, Canada
- Ottawa Institute of Systems Biology, Ottawa, ON, Canada
| | - Artem Cherkasov
- Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada
| | - Martina Crispo
- Unidad de Biotecnología en Animales de Laboratorio, Institut Pasteur de Montevideo, Montevideo, Uruguay.
| | - Gonzalo Moratorio
- Laboratorio de Virología Molecular, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
- Laboratorio de Evolución Experimental de Virus, Institut Pasteur de Montevideo, Montevideo, Uruguay.
| | - Geraldine Gueron
- Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
- Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina.
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11
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Zhu W, Zhou Y, Guo L, Feng S. Biological function of sialic acid and sialylation in human health and disease. Cell Death Discov 2024; 10:415. [PMID: 39349440 PMCID: PMC11442784 DOI: 10.1038/s41420-024-02180-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 09/08/2024] [Accepted: 09/12/2024] [Indexed: 10/02/2024] Open
Abstract
Sialic acids are predominantly found at the terminal ends of glycoproteins and glycolipids and play key roles in cellular communication and function. The process of sialylation, a form of post-translational modification, involves the covalent attachment of sialic acid to the terminal residues of oligosaccharides and glycoproteins. This modification not only provides a layer of electrostatic repulsion to cells but also serves as a receptor for various biological signaling pathways. Sialylation is involved in several pathophysiological processes. Given its multifaceted involvement in cellular functions, sialylation presents a promising avenue for therapeutic intervention. Current studies are exploring agents that target sialic acid residues on sialoglycans or the sialylation process. These efforts are particularly focused on the fields of cancer therapy, stroke treatment, antiviral strategies, and therapies for central nervous system disorders. In this review, we aimed to summarize the biological functions of sialic acid and the process of sialylation, explore their roles in various pathophysiological contexts, and discuss their potential applications in the development of novel therapeutics.
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Affiliation(s)
- Wengen Zhu
- Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Yue Zhou
- Department of Ophthalmology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Linjuan Guo
- Department of Cardiology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China.
| | - Shenghui Feng
- Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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12
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Tandon A, Santura A, Waldmann H, Pahl A, Czodrowski P. Identification of lysosomotropism using explainable machine learning and morphological profiling cell painting data. RSC Med Chem 2024; 15:2677-2691. [PMID: 39149097 PMCID: PMC11324048 DOI: 10.1039/d4md00107a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Accepted: 05/09/2024] [Indexed: 08/17/2024] Open
Abstract
Lysosomotropism is a phenomenon of diverse pharmaceutical interests because it is a property of compounds with diverse chemical structures and primary targets. While it is primarily reported to be caused by compounds having suitable lipophilicity and basicity values, not all compounds that fulfill such criteria are in fact lysosomotropic. Here, we use morphological profiling by means of the cell painting assay (CPA) as a reliable surrogate to identify lysosomotropism. We noticed that only 35% of the compound subset with matching physicochemical properties show the lysosomotropic phenotype. Based on a matched molecular pair analysis (MMPA), no key substructures driving lysosomotropism could be identified. However, using explainable machine learning (XML), we were able to highlight that higher lipophilicity, basicity, molecular weight, and lower topological polar surface area are among the important properties that induce lysosomotropism in the compounds of this subset.
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Affiliation(s)
- Aishvarya Tandon
- Department of Chemical Biology, Max-Planck-Institute of Molecular Physiology Otto-Hahn-Str. 11 Dortmund Germany
| | - Anna Santura
- Department of Chemistry, Johannes Gutenberg University Mainz Mainz Germany
| | - Herbert Waldmann
- Department of Chemical Biology, Max-Planck-Institute of Molecular Physiology Otto-Hahn-Str. 11 Dortmund Germany
| | - Axel Pahl
- Department of Chemical Biology, Max-Planck-Institute of Molecular Physiology Otto-Hahn-Str. 11 Dortmund Germany
| | - Paul Czodrowski
- Department of Chemistry, Johannes Gutenberg University Mainz Mainz Germany
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13
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Abisheva S, Rutskaya-Moroshan K, Nuranova G, Batyrkhan T, Abisheva A. Antimalarial Drugs at the Intersection of SARS-CoV-2 and Rheumatic Diseases: What Are the Potential Opportunities? MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1171. [PMID: 39064600 PMCID: PMC11279047 DOI: 10.3390/medicina60071171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 07/14/2024] [Accepted: 07/15/2024] [Indexed: 07/28/2024]
Abstract
Background and Objectives: The coronavirus disease of 2019 (COVID-19) pandemic has posed a serious threat to humanity and is considered a global health emergency. Antimalarial drugs (ADs) have been used in the treatment of immuno-inflammatory arthritis (IIA) and coronavirus infection (COVID-19). The aim of this review is to analyze the current knowledge about the immunomodulatory and antiviral mechanisms of action, characteristics of use, and side effects of antimalarial drugs. Material and Methods: A literature search was carried out using PubMed, MEDLINE, SCOPUS, and Google Scholar databases. The inclusion criteria were the results of randomized and cohort studies, meta-analyses, systematic reviews, and original full-text manuscripts in the English language containing statistically confirmed conclusions. The exclusion criteria were summary reports, newspaper articles, and personal messages. Qualitative methods were used for theoretical knowledge on antimalarial drug usage in AIRDs and SARS-CoV-2 such as a summarization of the literature and a comparison of the treatment methods. Results: The ADs were considered a "candidate" for the therapy of a new coronavirus infection due to mechanisms of antiviral activity, such as interactions with endocytic pathways, the prevention of glycosylation of the ACE2 receptors, blocking sialic acid receptors, and reducing the manifestations of cytokine storms. The majority of clinical trials suggest no role of antimalarial drugs in COVID-19 treatment or prevention. These circumstances do not allow for their use in the treatment and prevention of COVID-19. Conclusions: The mechanisms of hydroxychloroquine are related to potential cardiotoxic manifestations and demonstrate potential adverse effects when used for COVID-19. Furthermore, the need for high doses in the treatment of viral infections increases the likelihood of gastrointestinal side effects, the prolongation of QT, and retinopathy. Large randomized clinical trials (RCTs) have refuted the fact that there is a positive effect on the course and results of COVID-19.
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Affiliation(s)
- Saule Abisheva
- Department of Family Medicine №1, NJSC “Astana Medical University”, Astana 010000, Kazakhstan; (S.A.); (T.B.); (A.A.)
| | - Kristina Rutskaya-Moroshan
- Department of Family Medicine №1, NJSC “Astana Medical University”, Astana 010000, Kazakhstan; (S.A.); (T.B.); (A.A.)
| | - Gulnaz Nuranova
- Department of Children’s Diseases with Courses in Pulmonology and Nephrology, NJSC “Astana Medical University”, Astana 010000, Kazakhstan;
| | - Tansholpan Batyrkhan
- Department of Family Medicine №1, NJSC “Astana Medical University”, Astana 010000, Kazakhstan; (S.A.); (T.B.); (A.A.)
| | - Anilim Abisheva
- Department of Family Medicine №1, NJSC “Astana Medical University”, Astana 010000, Kazakhstan; (S.A.); (T.B.); (A.A.)
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14
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Liu Y, Meng Y, Zhang J, Gu L, Shen S, Zhu Y, Wang J. Pharmacology Progresses and Applications of Chloroquine in Cancer Therapy. Int J Nanomedicine 2024; 19:6777-6809. [PMID: 38983131 PMCID: PMC11232884 DOI: 10.2147/ijn.s458910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Accepted: 05/07/2024] [Indexed: 07/11/2024] Open
Abstract
Chloroquine is a common antimalarial drug and is listed in the World Health Organization Standard List of Essential Medicines because of its safety, low cost and ease of use. Besides its antimalarial property, chloroquine also was used in anti-inflammatory and antivirus, especially in antitumor therapy. A mount of data showed that chloroquine mainly relied on autophagy inhibition to exert its antitumor effects. However, recently, more and more researches have revealed that chloroquine acts through other mechanisms that are autophagy-independent. Nevertheless, the current reviews lacked a comprehensive summary of the antitumor mechanism and combined pharmacotherapy of chloroquine. So here we focused on the antitumor properties of chloroquine, summarized the pharmacological mechanisms of antitumor progression of chloroquine dependent or independent of autophagy inhibition. Moreover, we also discussed the side effects and possible application developments of chloroquine. This review provided a more systematic and cutting-edge knowledge involved in the anti-tumor mechanisms and combined pharmacotherapy of chloroquine in hope of carrying out more in-depth exploration of chloroquine and obtaining more clinical applications.
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Affiliation(s)
- Yanqing Liu
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, People's Republic of China
| | - Yuqing Meng
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, People's Republic of China
| | - Junzhe Zhang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, People's Republic of China
| | - Liwei Gu
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, People's Republic of China
| | - Shengnan Shen
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, People's Republic of China
| | - Yongping Zhu
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, People's Republic of China
| | - Jigang Wang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, People's Republic of China
- Department of Pharmacological Sciences, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore
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Velikova T, Valkov H, Aleksandrova A, Peshevska-Sekulovska M, Sekulovski M, Shumnalieva R. Harnessing immunity: Immunomodulatory therapies in COVID-19. World J Virol 2024; 13:92521. [PMID: 38984079 PMCID: PMC11229839 DOI: 10.5501/wjv.v13.i2.92521] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Revised: 04/02/2024] [Accepted: 04/11/2024] [Indexed: 06/24/2024] Open
Abstract
An overly exuberant immune response, characterized by a cytokine storm and uncontrolled inflammation, has been identified as a significant driver of severe coronavirus disease 2019 (COVID-19) cases. Consequently, deciphering the intricacies of immune dysregulation in COVID-19 is imperative to identify specific targets for intervention and modulation. With these delicate dynamics in mind, immunomodulatory therapies have emerged as a promising avenue for mitigating the challenges posed by COVID-19. Precision in manipulating immune pathways presents an opportunity to alter the host response, optimizing antiviral defenses while curbing deleterious inflammation. This review article comprehensively analyzes immunomodulatory interventions in managing COVID-19. We explore diverse approaches to mitigating the hyperactive immune response and its impact, from corticosteroids and non-steroidal drugs to targeted biologics, including anti-viral drugs, cytokine inhibitors, JAK inhibitors, convalescent plasma, monoclonal antibodies (mAbs) to severe acute respiratory syndrome coronavirus 2, cell-based therapies (i.e., CAR T, etc.). By summarizing the current evidence, we aim to provide a clear roadmap for clinicians and researchers navigating the complex landscape of immunomodulation in COVID-19 treatment.
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Affiliation(s)
- Tsvetelina Velikova
- Medical Faculty, Sofia University St. Kliment Ohridski, Sofia 1407, Bulgaria
| | - Hristo Valkov
- Department of Gastroenterology, University Hospital “Tsaritsa Yoanna-ISUL”, Medical University of Sofia, Sofia 1527, Bulgaria
| | | | - Monika Peshevska-Sekulovska
- Medical Faculty, Sofia University St. Kliment Ohridski, Sofia 1407, Bulgaria
- Department of Gastroenterology, University Hospital Lozenetz, Sofia 1407, Bulgaria
| | - Metodija Sekulovski
- Medical Faculty, Sofia University St. Kliment Ohridski, Sofia 1407, Bulgaria
- Department of Anesthesiology and Intensive Care, University Hospital Lozenetz, Sofia 1407, Bulgaria
| | - Russka Shumnalieva
- Medical Faculty, Sofia University St. Kliment Ohridski, Sofia 1407, Bulgaria
- Department of Rheumatology, Clinic of Rheumatology, University Hospital "St. Ivan Rilski", Medical University-Sofia, Sofia 1612, Bulgaria
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16
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Russo A, Patanè GT, Putaggio S, Lombardo GE, Ficarra S, Barreca D, Giunta E, Tellone E, Laganà G. Mechanisms Underlying the Effects of Chloroquine on Red Blood Cells Metabolism. Int J Mol Sci 2024; 25:6424. [PMID: 38928131 PMCID: PMC11203553 DOI: 10.3390/ijms25126424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 06/03/2024] [Accepted: 06/05/2024] [Indexed: 06/28/2024] Open
Abstract
Chloroquine (CQ) is a 4-aminoquinoline derivative largely employed in the management of malaria. CQ treatment exploits the drug's ability to cross the erythrocyte membrane, inhibiting heme polymerase in malarial trophozoites. Accumulation of CQ prevents the conversion of heme to hemozoin, causing its toxic buildup, thus blocking the survival of Plasmodium parasites. Recently, it has been reported that CQ is able to exert antiviral properties, mainly against HIV and SARS-CoV-2. This renewed interest in CQ treatment has led to the development of new studies which aim to explore its side effects and long-term outcome. Our study focuses on the effects of CQ in non-parasitized red blood cells (RBCs), investigating hemoglobin (Hb) functionality, the anion exchanger 1 (AE1) or band 3 protein, caspase 3 and protein tyrosine phosphatase 1B (PTP-1B) activity, intra and extracellular ATP levels, and the oxidative state of RBCs. Interestingly, CQ influences the functionality of both Hb and AE1, the main RBC proteins, affecting the properties of Hb oxygen affinity by shifting the conformational structure of the molecule towards the R state. The influence of CQ on AE1 flux leads to a rate variation of anion exchange, which begins at a concentration of 2.5 μM and reaches its maximum effect at 20 µM. Moreover, a significant decrease in intra and extracellular ATP levels was observed in RBCs pre-treated with 10 µM CQ vs. erythrocytes under normal conditions. This effect is related to the PTP-1B activity which is reduced in RBCs incubated with CQ. Despite these metabolic alterations to RBCs caused by exposure to CQ, no signs of variations in oxidative state or caspase 3 activation were recorded. Our results highlight the antithetical effects of CQ on the functionality and metabolism of RBCs, and encourage the development of new research to better understand the multiple potentiality of the drug.
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Affiliation(s)
| | - Giuseppe Tancredi Patanè
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy; (G.T.P.); (S.P.); (S.F.); (E.T.); (G.L.)
| | - Stefano Putaggio
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy; (G.T.P.); (S.P.); (S.F.); (E.T.); (G.L.)
| | | | - Silvana Ficarra
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy; (G.T.P.); (S.P.); (S.F.); (E.T.); (G.L.)
| | - Davide Barreca
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy; (G.T.P.); (S.P.); (S.F.); (E.T.); (G.L.)
| | - Elena Giunta
- Virology and Microbiology AOOR Papardo-Piemonte, 98166 Messina, Italy;
| | - Ester Tellone
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy; (G.T.P.); (S.P.); (S.F.); (E.T.); (G.L.)
| | - Giuseppina Laganà
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy; (G.T.P.); (S.P.); (S.F.); (E.T.); (G.L.)
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17
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Sari H, Putri HH, Paksi PW, Hidayat G, Amelia SR, Sundari CDD, Rachmawati H, Ivansyah AL, Muttaqien F, Iskandar F. Theoretical Investigation of the Green-Synthesized Carbon-Based Nanomaterial Potential as Inhibitors of ACE2 for Blocking SARS-CoV-2 Binding. ACS OMEGA 2024; 9:16701-16715. [PMID: 38617634 PMCID: PMC11007854 DOI: 10.1021/acsomega.4c00759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 03/01/2024] [Accepted: 03/12/2024] [Indexed: 04/16/2024]
Abstract
Since the emergence of SARS-CoV-2 in 2020, the world has faced a global pandemic, emphasizing the urgent need for effective treatments to combat COVID-19. This study explores the use of green-synthesized carbon-based nanomaterials as potential inhibitors of ACE2, a critical receptor for SARS-CoV-2 entry into host cells. Specifically, the study examines four carbon-based nanomaterials, namely, CD1, CD2, CD3, and CD4 in amino, graphitic, pyridinic, and pyrrolic forms, respectively, synthesized from curcumin, to investigate their binding affinity with ACE2. Molecular docking studies revealed that CD3 (pyridinic form) exhibited the highest binding affinity with ACE2, surpassing that of the control compound, curcumin. Notably, CD3 formed hydrophobic interactions and hydrogen bonds with key ACE2 residues, suggesting its potential to block the binding of SARS-CoV-2 to human cells. Moreover, molecular dynamics simulations demonstrated the stability of these ligand-ACE2 complexes, further supporting the promise of CD3 as an inhibitor. Quantum chemical analyses, including frontier molecular orbitals, natural bond orbital analysis, and the quantum theory of atoms in molecules, unveiled valuable insights into the reactivity and interaction strengths of these ligands. CD3 exhibited desirable chemical properties, signifying its suitability for therapeutic development. The study's findings suggest that green-synthesized carbon-based nanomaterials, particularly CD3, have the potential to serve as effective inhibitors of ACE2, offering a promising avenue for the development of treatments against COVID-19. Further experimental validation is warranted to advance these findings and establish new therapies for the ongoing global pandemic.
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Affiliation(s)
- Harsiwi
Candra Sari
- Master
Program in Computational Science, Faculty of Mathematics and Natural
Sciences, Institut Teknologi Bandung, Jalan Ganesha 10, Bandung, West Java 40132, Indonesia
| | - Haliza Hasnia Putri
- Master
Program in Computational Science, Faculty of Mathematics and Natural
Sciences, Institut Teknologi Bandung, Jalan Ganesha 10, Bandung, West Java 40132, Indonesia
| | - Pinantun Wiguna
Kusuma Paksi
- Master
Program in Computational Science, Faculty of Mathematics and Natural
Sciences, Institut Teknologi Bandung, Jalan Ganesha 10, Bandung, West Java 40132, Indonesia
| | - Gabriel Hidayat
- Master
Program in Computational Science, Faculty of Mathematics and Natural
Sciences, Institut Teknologi Bandung, Jalan Ganesha 10, Bandung, West Java 40132, Indonesia
| | - Silmi Rahma Amelia
- Master
Program in Computational Science, Faculty of Mathematics and Natural
Sciences, Institut Teknologi Bandung, Jalan Ganesha 10, Bandung, West Java 40132, Indonesia
| | - Citra Deliana Dewi Sundari
- Department
of Chemistry, Institut Teknologi Bandung, Jalan Ganesha 10, Bandung, West Java 40132, Indonesia
- Chemistry
Education, Universitas Islam Negeri Sunan
Gunung Djati Bandung, Jl. A. H. Nasution No. 105, Bandung, West Java 40614, Indonesia
| | - Heni Rachmawati
- School
of Pharmacy, Institut Teknologi Bandung, Jalan Ganesha 10, Bandung, West Java 40132, Indonesia
- Research
Center for Nanosciences and Nanotechnology, Institut Teknologi Bandung, Jalan Ganesha 10, Bandung, West Java 40132, Indonesia
| | - Atthar Luqman Ivansyah
- Master
Program in Computational Science, Faculty of Mathematics and Natural
Sciences, Institut Teknologi Bandung, Jalan Ganesha 10, Bandung, West Java 40132, Indonesia
- Department
of Physics, Institut Teknologi Bandung, Jalan Ganesha 10, Bandung, West Java 40132, Indonesia
| | - Fahdzi Muttaqien
- Master
Program in Computational Science, Faculty of Mathematics and Natural
Sciences, Institut Teknologi Bandung, Jalan Ganesha 10, Bandung, West Java 40132, Indonesia
- Department
of Physics, Institut Teknologi Bandung, Jalan Ganesha 10, Bandung, West Java 40132, Indonesia
| | - Ferry Iskandar
- Research
Center for Nanosciences and Nanotechnology, Institut Teknologi Bandung, Jalan Ganesha 10, Bandung, West Java 40132, Indonesia
- Department
of Physics, Institut Teknologi Bandung, Jalan Ganesha 10, Bandung, West Java 40132, Indonesia
- Collaboration
Research Center for Advanced Energy Materials, National Research and Innovation Agency - Institut Teknologi Bandung, Jl. Ganesha 10∇, Bandung 40132, Indonesia
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18
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Deshmukh R, Harwansh RK, Garg A, Mishra S, Agrawal R, Jangde R. COVID-19: Recent Insight in Genomic Feature, Pathogenesis, Immunological Biomarkers, Treatment Options and Clinical Updates on SARS-CoV-2. Curr Genomics 2024; 25:69-87. [PMID: 38751601 PMCID: PMC11092912 DOI: 10.2174/0113892029291098240129113500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 01/11/2024] [Accepted: 01/17/2024] [Indexed: 05/18/2024] Open
Abstract
SARS-CoV-2 is a highly contagious and transmissible viral infection that first emerged in 2019 and since then has sparked an epidemic of severe respiratory problems identified as "coronavirus disease 2019" (COVID-19) that causes a hazard to human life and safety. The virus developed mainly from bats. The current epidemic has presented a significant warning to life across the world by showing mutation. There are different tests available for testing Coronavirus, and RT-PCR is the best, giving more accurate results, but it is also time-consuming. There are different options available for treating n-CoV-19, which include medications such as Remdesivir, corticosteroids, plasma therapy, Dexamethasone therapy, etc. The development of vaccines such as BNT126b2, ChAdOX1, mRNA-1273 and BBIBP-CorV has provided great relief in dealing with the virus as they decreased the mortality rate. BNT126b2 and ChAdOX1 are two n-CoV vaccines found to be most effective in controlling the spread of infection. In the future, nanotechnology-based vaccines and immune engineering techniques can be helpful for further research on Coronavirus and treatment of this deadly virus. The existing knowledge about the existence of SARS-CoV-2, along with its variants, is summarized in this review. This review, based on recently published findings, presents the core genetics of COVID-19, including heritable characteristics, pathogenesis, immunological biomarkers, treatment options and clinical updates on the virus, along with patents.
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Affiliation(s)
- Rohitas Deshmukh
- Department of Pharmaceutics, Institute of Pharmaceutical Research, GLA University, Mathura, 281406, Uttar Pradesh, India
| | - Ranjit Kumar Harwansh
- Department of Pharmaceutics, Institute of Pharmaceutical Research, GLA University, Mathura, 281406, Uttar Pradesh, India
| | - Akash Garg
- Department of Pharmaceutics, Rajiv Academy for Pharmacy, NH-2, Mathura, Delhi Road, Chhatikara, 281001, Uttar Pradesh, India
| | - Sakshi Mishra
- Department of Pharmaceutics, Institute of Pharmaceutical Research, GLA University, Mathura, 281406, Uttar Pradesh, India
| | - Rutvi Agrawal
- Department of Pharmaceutics, Rajiv Academy for Pharmacy, NH-2, Mathura, Delhi Road, Chhatikara, 281001, Uttar Pradesh, India
| | - Rajendra Jangde
- Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, 492010, India
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Chen B, Li F, Lin Y, Yang L, Wei W, Ni BJ, Chen X. Degradation of Chloroquine by Ammonia-Oxidizing Bacteria: Performance, Mechanisms, and Associated Impact on N 2O Production. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2024; 58:4662-4669. [PMID: 38422482 DOI: 10.1021/acs.est.3c09928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/02/2024]
Abstract
Since the mass production and extensive use of chloroquine (CLQ) would lead to its inevitable discharge, wastewater treatment plants (WWTPs) might play a key role in the management of CLQ. Despite the reported functional versatility of ammonia-oxidizing bacteria (AOB) that mediate the first step for biological nitrogen removal at WWTP (i.e., partial nitrification), their potential capability to degrade CLQ remains to be discovered. Therefore, with the enriched partial nitrification sludge, a series of dedicated batch tests were performed in this study to verify the performance and mechanisms of CLQ biodegradation under the ammonium conditions of mainstream wastewater. The results showed that AOB could degrade CLQ in the presence of ammonium oxidation activity, but the capability was limited by the amount of partial nitrification sludge (∼1.1 mg/L at a mixed liquor volatile suspended solids concentration of 200 mg/L). CLQ and its biodegradation products were found to have no significant effect on the ammonium oxidation activity of AOB while the latter would promote N2O production through the AOB denitrification pathway, especially at relatively low DO levels (≤0.5 mg-O2/L). This study provided valuable insights into a more comprehensive assessment of the fate of CLQ in the context of wastewater treatment.
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Affiliation(s)
- Bokai Chen
- College of Environment and Safety Engineering, Fuzhou University, Fuzhou 350116, China
| | - Fuyi Li
- College of Environment and Safety Engineering, Fuzhou University, Fuzhou 350116, China
| | - Yinghui Lin
- College of Environment and Safety Engineering, Fuzhou University, Fuzhou 350116, China
| | - Linyan Yang
- School of Resources and Environmental Engineering, East China University of Science and Technology, Shanghai 200237, China
| | - Wei Wei
- Centre for Technology in Water and Wastewater, School of Civil and Environmental Engineering, University of Technology Sydney, Sydney, New South Wales 2007, Australia
| | - Bing-Jie Ni
- Centre for Technology in Water and Wastewater, School of Civil and Environmental Engineering, University of Technology Sydney, Sydney, New South Wales 2007, Australia
| | - Xueming Chen
- College of Environment and Safety Engineering, Fuzhou University, Fuzhou 350116, China
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20
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Zhao X, Wu H, Li S, Gao C, Wang J, Ge L, Song Z, Ni B, You Y. The impact of the COVID-19 pandemic on SLE. Mod Rheumatol 2024; 34:247-264. [PMID: 36961736 DOI: 10.1093/mr/road030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 02/21/2023] [Accepted: 03/11/2023] [Indexed: 03/25/2023]
Abstract
Little is known about the association between coronavirus disease 2019 (COVID-19) and autoimmune diseases, especially in the case of systemic lupus erythematosus (SLE). SLE patients met with many questions during the pandemic in COVID-19, such as how to minimize risk of infection, the complex pathological features and cytokine profiles, diagnosis and treatment, rational choice of drugs and vaccine, good nursing, psychological supervision, and so on. In this study, we review and discuss the multifaceted effects of the COVID-19 pandemic on patients living with SLE using the available literature. Cross-talk in implicated inflammatory pathways/mechanisms exists between SLE and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and SARS-CoV-2 displays similar clinical characteristics and immuno-inflammatory responses to SLE. Current epidemiological data inadequately assess the risk and severity of COVID-19 infection in patients with SLE. More evidence has shown that hydroxychloroquine and chloroquine cannot prevent COVID-19. During the pandemic, patients with SLE had a higher rate of hospitalization. Vaccination helps to reduce the risk of infection. Several therapies for patients with SLE infected with COVID-19 are discussed. The cases in the study can provide meaningful information for clinical diagnosis and management. Our main aim is to help preventing infection and highlight treatment options for patients with SLE infected with COVID-19.
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Affiliation(s)
- Xingwang Zhao
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Haohao Wu
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Shifei Li
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Cuie Gao
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Juan Wang
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Lan Ge
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Zhiqiang Song
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Bing Ni
- Department of Pathophysiology, College of High Altitude Military Medicine, Army Medical University (Third Military Medical University), Chongqing, China
| | - Yi You
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
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22
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Mia ME, Howlader M, Akter F, Hossain MM. Preclinical and Clinical Investigations of Potential Drugs and Vaccines for COVID-19 Therapy: A Comprehensive Review With Recent Update. CLINICAL PATHOLOGY (THOUSAND OAKS, VENTURA COUNTY, CALIF.) 2024; 17:2632010X241263054. [PMID: 39070952 PMCID: PMC11282570 DOI: 10.1177/2632010x241263054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Accepted: 06/03/2024] [Indexed: 07/30/2024]
Abstract
The COVID-19 pandemic-led worldwide healthcare crisis necessitates prompt societal, ecological, and medical efforts to stop or reduce the rising number of fatalities. Numerous mRNA based vaccines and vaccines for viral vectors have been licensed for use in emergencies which showed 90% to 95% efficacy in preventing SARS-CoV-2 infection. However, safety issues, vaccine reluctance, and skepticism remain major concerns for making mass vaccination a successful approach to treat COVID-19. Hence, alternative therapeutics is needed for eradicating the global burden of COVID-19 from developed and low-resource countries. Repurposing current medications and drug candidates could be a more viable option for treating SARS-CoV-2 as these therapies have previously passed a number of significant checkpoints for drug development and patient care. Besides vaccines, this review focused on the potential usage of alternative therapeutic agents including antiviral, antiparasitic, and antibacterial drugs, protease inhibitors, neuraminidase inhibitors, and monoclonal antibodies that are currently undergoing preclinical and clinical investigations to assess their effectiveness and safety in the treatment of COVID-19. Among the repurposed drugs, remdesivir is considered as the most promising agent, while favipiravir, molnupiravir, paxlovid, and lopinavir/ritonavir exhibited improved therapeutic effects in terms of elimination of viruses. However, the outcomes of treatment with oseltamivir, umifenovir, disulfiram, teicoplanin, and ivermectin were not significant. It is noteworthy that combining multiple drugs as therapy showcases impressive effectiveness in managing individuals with COVID-19. Tocilizumab is presently employed for the treatment of patients who exhibit COVID-19-related pneumonia. Numerous antiviral drugs such as galidesivir, griffithsin, and thapsigargin are under clinical trials which could be promising for treating COVID-19 individuals with severe symptoms. Supportive treatment for patients of COVID-19 may involve the use of corticosteroids, convalescent plasma, stem cells, pooled antibodies, vitamins, and natural substances. This study provides an updated progress in SARS-CoV-2 medications and a crucial guide for inventing novel interventions against COVID-19.
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Affiliation(s)
- Md. Easin Mia
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Mithu Howlader
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Farzana Akter
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Md. Murad Hossain
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh
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Chavda V, Yadav D, Parmar H, Brahmbhatt R, Patel B, Madhwani K, Jain M, Song M, Patel S. A Narrative Overview of Coronavirus Infection: Clinical Signs and Symptoms, Viral Entry and Replication, Treatment Modalities, and Management. Curr Top Med Chem 2024; 24:1883-1916. [PMID: 38859776 DOI: 10.2174/0115680266296095240529114058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Revised: 04/18/2024] [Accepted: 04/26/2024] [Indexed: 06/12/2024]
Abstract
The global pandemic known as coronavirus disease (COVID-19) is causing morbidity and mortality on a daily basis. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV- -2) virus has been around since December 2019 and has infected a high number of patients due to its idiopathic pathophysiology and rapid transmission. COVID-19 is now deemed a newly identified "syndrome" condition since it causes a variety of unpleasant symptoms and systemic side effects following the pandemic. Simultaneously, it always becomes potentially hazardous when new variants develop during evolution. Its random viral etiology prevents accurate and suitable therapy. Despite the fact that multiple preclinical and research studies have been conducted to combat this lethal virus, and various therapeutic targets have been identified, the precise course of therapy remains uncertain. However, just a few drugs have shown efficacy in treating this viral infection in its early stages. Currently, several medicines and vaccinations have been licensed following clinical trial research, and many countries are competing to find the most potent and effective immunizations against this highly transmissible illness. For this narrative review, we used PubMed, Google Scholar, and Scopus to obtain epidemiological data, pre-clinical and clinical trial outcomes, and recent therapeutic alternatives for treating COVID-19 viral infection. In this study, we discussed the disease's origin, etiology, transmission, current advances in clinical diagnostic technologies, different new therapeutic targets, pathophysiology, and future therapy options for this devastating virus. Finally, this review delves further into the hype surrounding the SARS-CoV-2 illness, as well as present and potential COVID-19 therapies.
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Affiliation(s)
- Vishal Chavda
- Department of Pathology, Stanford School of Medicine, Stanford University Medical Center, Palo Alto94305, CA, USA
- Department of Medicine, Multispeciality, Trauma and ICCU Center, Sardar Hospital, Ahmedabad, 382352, Gujarat, India
| | - Dhananjay Yadav
- Department of Life Science, Yeungnam University, South Korea
| | - Harisinh Parmar
- Department of Neurosurgery, Krishna institute of medical sciences, Karad, Maharashtra, India
| | - Raxit Brahmbhatt
- Department of Medicine, Multispeciality, Trauma and ICCU Center, Sardar Hospital, Ahmedabad, 382352, Gujarat, India
| | - Bipin Patel
- Department of Medicine, Multispeciality, Trauma and ICCU Center, Sardar Hospital, Ahmedabad, 382352, Gujarat, India
| | - Kajal Madhwani
- Department of Life Science, University of Westminster, London, W1B 2HW, United Kingdom
| | - Meenu Jain
- Gajra Raja Medical College, Gwalior, 474009, Madhya Pradesh, India
| | - Minseok Song
- Department of Life Science, Yeungnam University, South Korea
| | - Snehal Patel
- Department of Pharmacology, Nirma University, Ahmedabad, 382481, Gujarat, India
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24
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Ortiz-Prado E, Izquierdo-Condoy JS, Mora C, Vasconez-Gonzalez J, Fernandez-Naranjo R. Poor regulation, desperation, and misinformation, a countrywide analysis of self-medication and prescription patterns in Ecuador during the COVID-19 pandemic. Res Social Adm Pharm 2023; 19:1579-1589. [PMID: 37659922 DOI: 10.1016/j.sapharm.2023.08.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 08/23/2023] [Accepted: 08/28/2023] [Indexed: 09/04/2023]
Abstract
BACKGROUND The rapid spread of the SARS-CoV-2 virus during the early phase of the pandemic led to an unprecedented global health crisis. Various factors have influenced self-medication practices among the general population and unsubstantiated prescribing practices among healthcare professionals. OBJECTIVE This study aimed to describe trends in the purchase and sale of medicines during the COVID-19 pandemic period (2020-2022) in Ecuador, by comparing them with pre-pandemic periods. METHODS In this study, a cross-sectional design was employed to conduct a comprehensive analysis of 28 pharmacological groups, categorized according to the Anatomical Therapeutic Chemical Classification (ATC). Utilizing an integrated drug consumption database, the study examined physician prescribing data, medicine usage, and spending levels in Ecuador during the COVID-19 pandemic. The analysis involved computing absolute differences in monthly resolution, calculating excessive expenditure in comparison to previous yearly averages, and using Defined Daily Dose (DDD) methodology for internationally comparable results. Furthermore, a correlation analysis was performed to investigate potential associations between prescribed and consumed medicines and the number of new cases and deaths. RESULTS In Ecuador, the average yearly expenditure among these groups prior to the pandemic (2017-2019) amounted to $150,646,206 USD, whereas during 2020 and 2021, the same groups represented a total expenditure of $228,327,210, reflecting a significant increase. The excess expenditure during this period reached 51.4%, equivalent to $77,681,004 USD. Notably, 13% of this expenditure consisted of Over the Counter (OTC) Medicines. The study also identified a remarkable surge in sales of ivermectin, which increased by 2,057%, and hydroxychloroquine, which increased by 171%, as measured by DDD. CONCLUSIONS This study highlights the substantial consumption of medicines by the population in Ecuador during the pandemic. It is concerning that many medications were sold without proven therapeutic indications, indicating that misinformation and desperation may have led to improper prescribing by physicians and patients resorting to ineffective drugs. Moreover, since the sale of these therapeutic drugs requires a prescription, poor regulation, and a lack of control within pharmacies likely contributed to such practices.
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Affiliation(s)
- Esteban Ortiz-Prado
- One Health Research Group, Faculty of Medicine, Universidad de Las Américas, Quito, 170125, Ecuador.
| | - Juan S Izquierdo-Condoy
- One Health Research Group, Faculty of Medicine, Universidad de Las Américas, Quito, 170125, Ecuador
| | - Carla Mora
- Medical Department, Quifatex, Quito, 170138, Ecuador
| | - Jorge Vasconez-Gonzalez
- One Health Research Group, Faculty of Medicine, Universidad de Las Américas, Quito, 170125, Ecuador
| | - Raúl Fernandez-Naranjo
- One Health Research Group, Faculty of Medicine, Universidad de Las Américas, Quito, 170125, Ecuador
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Vieux N, Perrier Q, Bedouch P, Epaulard O. Much ado about nothing? Discrepancy between the available data on the antiviral effect of hydroxychloroquine in March 2020 and its inclusion in COVID-19 clinical trials and outpatient prescriptions. Public Health 2023; 225:35-44. [PMID: 37918175 DOI: 10.1016/j.puhe.2023.09.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 07/10/2023] [Accepted: 09/24/2023] [Indexed: 11/04/2023]
Abstract
OBJECTIVES Many of the 2020 COVID-19 clinical trials included an (hydroxy)chloroquine ((H)CQ) arm. We aimed to juxtapose the state of science before April 2020 regarding the benefits of (H)CQ for viral infections with the number and size of the clinical trials studying (H)CQ and the volume of (H)CQ dispensed in France. STUDY DESIGN We identified and analysed published scientific material regarding the antiviral activity of (H)CQ and publicly available data regarding clinical trials and drug dispensation in France. METHODS We conducted a review of scientific publications available before April 2020 and a systematic analysis of COVID-19 clinical trials featuring (H)CQ registered on clinicaltrials.gov. RESULTS Before April 2020, 894 scientific publications mentioning (H)CQ for viruses other than coronaviruses were available, including 35 in vitro studies (reporting an inconstant inhibition of viral replication), 11 preclinical studies (reporting no or disputable positive effects), and 32 clinical trials (reporting no or disputable positive effects). Moreover, 67 publications on (H)CQ and coronavirus infections were available, including 12 in vitro studies (reporting an inconstant inhibition of viral replication), two preclinical studies (reporting contradictory results), and no clinical trials. Meanwhile, 253 therapeutic clinical trials featuring an HCQ arm were registered in 2020, intending to enrol 246,623 patients. CONCLUSIONS The number and size of (H)CQ clinical trials for COVID-19 launched in 2020 were not supported by the literature published before April 2020.
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Affiliation(s)
- N Vieux
- Pôle Pharmacie, Université Grenoble Alpes, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France
| | - Q Perrier
- Pôle Pharmacie, Université Grenoble Alpes, Centre Hospitalier Universitaire Grenoble Alpes, Laboratory of Fundamental and Applied Bioenergetic (LBFA), INSERM U1055, Grenoble, France
| | - P Bedouch
- Pôle Pharmacie, Université Grenoble Alpes, Centre Hospitalier Universitaire Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, CHU Grenoble Alpes, TIMC, 38000 Grenoble, France
| | - O Epaulard
- Infectious Disease Department, Université Grenoble Alpes, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France; Groupe de Recherche en Infectiologie Clinique, CIC-1406, INSERM-UGA-CHUGA, France.
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Saleki K, Alijanizadeh P, Azadmehr A. Is neuropilin-1 the neuroimmune initiator of multi-system hyperinflammation in COVID-19? Biomed Pharmacother 2023; 167:115558. [PMID: 37748412 DOI: 10.1016/j.biopha.2023.115558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 09/16/2023] [Accepted: 09/19/2023] [Indexed: 09/27/2023] Open
Abstract
A major immunopathological feature of Coronavirus disease-2019 (COVID-19) is excessive inflammation in the form of "cytokine storm". The storm is characterized by injurious levels of cytokines which form a complicated network damaging different organs, including the lungs and the brain. The main starter of "cytokine network" hyperactivation in COVID-19 has not been discovered yet. Neuropilins (NRPs) are transmembrane proteins that act as neuronal guidance and angiogenesis modulators. The crucial function of NRPs in forming the nervous and vascular systems has been well-studied. NRP1 and NRP2 are the two identified homologs of NRP. NRP1 has been shown as a viral entry pathway for SARS-CoV2, which facilitates neuroinvasion by the virus within the central or peripheral nervous systems. These molecules directly interact with various COVID-19-related molecules, such as specific regions of the spike protein (major immune element of SARS-CoV2), vascular endothelial growth factor (VEGF) receptors, VEGFR1/2, and ANGPTL4 (regulator of vessel permeability and integrity). NRPs mainly play a role in hyperinflammatory injury of the CNS and lungs, and also the liver, kidney, pancreas, and heart in COVID-19 patients. New findings have suggested NRPs good candidates for pharmacotherapy of COVID-19. However, therapeutic targeting of NRP1 in COVID-19 is still in the preclinical phase. This review presents the implications of NRP1 in multi-organ inflammation-induced injury by SARS-CoV2 and provides insights for NRP1-targeting treatments for COVID-19 patients.
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Affiliation(s)
- Kiarash Saleki
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran; Department of e-Learning, Virtual School of Medical Education and Management, Shahid Beheshti University of Medical Sciences(SBMU), Tehran, Iran; USERN Office, Babol University of Medical Sciences, Babol, Iran
| | - Parsa Alijanizadeh
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran; USERN Office, Babol University of Medical Sciences, Babol, Iran
| | - Abbas Azadmehr
- Immunology Department, Babol University of Medical Sciences, Babol, Iran; Cellular and Molecular Biology Research Center Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
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Danjuma MI, Sayed R, Aboughalia M, Hassona A, Elsayed BS, Elshafei M, Elzouki A. Does colchicine reduce mortality in patients with COVID-19 clinical syndrome? An umbrella review of published meta-analyses. Heliyon 2023; 9:e20155. [PMID: 37767472 PMCID: PMC10520783 DOI: 10.1016/j.heliyon.2023.e20155] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 07/25/2023] [Accepted: 09/13/2023] [Indexed: 09/29/2023] Open
Abstract
Background Despite significant improvements in both treatment and prevention strategies, as well as multiple commissioned reviews, there remains uncertainty regarding the survival benefit of repurposed drugs such as colchicine in patients with Coronavirus Disease 2019 (COVID-19) clinical syndrome. Methods In this umbrella review, we carried out a comprehensive search of PubMed, EMBASE, Cochrane Database of Systematic Reviews, Science Citation Index, and the Database of Abstracts of Reviews of Effectiveness between January 1, 2020 and January 31, 2023 for systematic reviews and meta-analyses evaluating the mortality-reducing benefits of colchicine in patients with COVID-19. This was to ascertain the exact relationship between colchicine exposure and mortality outcomes in these cohorts of patients. We utilized A Measurement Tool to Assess systematic Reviews-2 (AMSTAR-2) to conduct an exhaustive methodological quality and risk of bias assessment of the included reviews. Results We included eighteen meta-analyses (n = 199,932 participants) in this umbrella review. Colchicine exposure was associated with an overall reduction of about 32% in the risk of mortality (odds ratio 0.68, confidence interval [CI] 0.58-0.78; I2 = 94%, p = 0.001). Further examination of pooled estimates of mortality outcomes by the quality effects model (corrected for the methodological quality and risk of bias of the constituent reviews) reported similar point estimates (OR 0.73; CI 0.59 to 0.91; I2 = 94%). Conclusion In a pooled umbrella evaluation of published meta-analyses of COVID-19 patient cohorts, exposure to colchicine was associated with a reduction in overall mortality. Although it remains uncertain if this effect could potentially be attenuated or augmented by COVID-19 vaccination.
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Affiliation(s)
- Mohammed I. Danjuma
- Department of Internal Medicine, Hamad Medical Corporation, Doha, Qatar
- Department of Internal Medicine, Weill Cornell College of Medicine, New York, Doha, Qatar
- NHS Grampian (Dr. Grays Hospital), Scotland, UK
| | - Rana Sayed
- Department of Internal Medicine, Qatar University College of Medicine, Doha, Qatar
| | - Maryam Aboughalia
- Department of Internal Medicine, Qatar University College of Medicine, Doha, Qatar
| | - Aseel Hassona
- Department of Internal Medicine, Qatar University College of Medicine, Doha, Qatar
| | - Basant Selim Elsayed
- Department of Internal Medicine, Qatar University College of Medicine, Doha, Qatar
| | | | - Abdelnaser Elzouki
- Department of Internal Medicine, Hamad Medical Corporation, Doha, Qatar
- Department of Internal Medicine, Weill Cornell College of Medicine, New York, Doha, Qatar
- Department of Internal Medicine, Qatar University College of Medicine, Doha, Qatar
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Awad AM, Hansen K, Del Rio D, Flores D, Barghash RF, Kakkola L, Julkunen I, Awad K. Insights into COVID-19: Perspectives on Drug Remedies and Host Cell Responses. Biomolecules 2023; 13:1452. [PMID: 37892134 PMCID: PMC10604481 DOI: 10.3390/biom13101452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 09/19/2023] [Accepted: 09/21/2023] [Indexed: 10/29/2023] Open
Abstract
In light of the COVID-19 global pandemic caused by SARS-CoV-2, ongoing research has centered on minimizing viral spread either by stopping viral entry or inhibiting viral replication. Repurposing antiviral drugs, typically nucleoside analogs, has proven successful at inhibiting virus replication. This review summarizes current information regarding coronavirus classification and characterization and presents the broad clinical consequences of SARS-CoV-2 activation of the angiotensin-converting enzyme 2 (ACE2) receptor expressed in different human cell types. It provides publicly available knowledge on the chemical nature of proposed therapeutics and their target biomolecules to assist in the identification of potentially new drugs for the treatment of SARS-CoV-2 infection.
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Affiliation(s)
- Ahmed M. Awad
- Department of Chemistry, California State University Channel Islands, Camarillo, CA 93012, USA
| | - Kamryn Hansen
- Department of Chemistry, California State University Channel Islands, Camarillo, CA 93012, USA
| | - Diana Del Rio
- Department of Chemistry, California State University Channel Islands, Camarillo, CA 93012, USA
| | - Derek Flores
- Department of Chemistry, California State University Channel Islands, Camarillo, CA 93012, USA
| | - Reham F. Barghash
- Institute of Chemical Industries Research, National Research Centre, Dokki, Cairo 12622, Egypt
| | - Laura Kakkola
- Institute of Biomedicine, Faculty of Medicine, University of Turku, 20014 Turku, Finland
| | - Ilkka Julkunen
- Institute of Biomedicine, Faculty of Medicine, University of Turku, 20014 Turku, Finland
- Clinical Microbiology, Turku University Hospital, 20521 Turku, Finland
| | - Kareem Awad
- Institute of Biomedicine, Faculty of Medicine, University of Turku, 20014 Turku, Finland
- Department of Therapeutic Chemistry, Institute of Pharmaceutical and Drug Industries Research, National Research Center, Dokki, Cairo 12622, Egypt
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Liu J, Hu Y, Li X, Xiao C, Shi Y, Chen Y, Cheng J, Zhu X, Wang G, Xie J. High-efficient degradation of chloroquine phosphate by oxygen doping MoS 2 co-catalytic Fenton reaction. JOURNAL OF HAZARDOUS MATERIALS 2023; 458:131894. [PMID: 37352777 DOI: 10.1016/j.jhazmat.2023.131894] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 05/30/2023] [Accepted: 06/17/2023] [Indexed: 06/25/2023]
Abstract
To degrade the antiviral and antimalarial drug chloroquine phosphate (CQP), an oxygen doping MoS2 nanoflower (O-MoS2-230) co-catalyst was prepared by a hydrothermal method to construct an O-MoS2-230 co-catalytic Fenton system (O-MoS2-230/Fenton) without pH adjustment (initial pH 5.4). Remarkable CQP degradation efficiency (99.5 %) could be achieved in 10 min under suitable conditions ([co-catalyst] = 0.2 g L-1, [Fe2+]0 = 70 μM, [H2O2]0 = 0.4 mM) with a reaction rate constant of 0.24 min-1, which was 4.8 times that of MoS2 co-catalytic Fenton system (MoS2/Fenton). Compared to MoS2/Fenton, the system had 1.5 times more Fe2+ (28.4 μM) and showed a 24.0 % increase in H2O2 activation efficiency, reaching 50.0 %. The electron paramagnetic resonance (EPR) determinations and active species trapping experimental data revealed that •OH and 1O2 were responsible for CQP degradation. The combination of experiments and density functional theory (DFT) calculation demonstrates that O doping in MoS2 modifies the surface charge distribution, leading to an increase in its conductivity, thus accelerating the Fe3+/Fe2+ cycle and promoting reactive oxygen species (ROS) generation. Furthermore, O-MoS2-230/Fenton system exhibited excellent stability. This work reveals the degradation mechanism of accelerated Fe3+/Fe2+ cycle and abundant ROS in the O-MoS2-230/Fenton system and provides a promising technology for antibiotic pollutant degradation.
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Affiliation(s)
- Jingyu Liu
- School of Environment and Energy, South China University of Technology, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China; The Key Lab of Pollution Control and Ecosystem Restoration in Industry Clusters, Ministry of Education, South China University of Technology, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China
| | - Yongyou Hu
- School of Environment and Energy, South China University of Technology, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China; The Key Lab of Pollution Control and Ecosystem Restoration in Industry Clusters, Ministry of Education, South China University of Technology, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China.
| | - Xian Li
- School of Environment and Energy, South China University of Technology, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China; The Key Lab of Pollution Control and Ecosystem Restoration in Industry Clusters, Ministry of Education, South China University of Technology, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China
| | - Chun Xiao
- School of Environment and Energy, South China University of Technology, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China; The Key Lab of Pollution Control and Ecosystem Restoration in Industry Clusters, Ministry of Education, South China University of Technology, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China
| | - Yueyue Shi
- School of Environment and Energy, South China University of Technology, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China; The Key Lab of Pollution Control and Ecosystem Restoration in Industry Clusters, Ministry of Education, South China University of Technology, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China
| | - Yuancai Chen
- School of Environment and Energy, South China University of Technology, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China; The Key Lab of Pollution Control and Ecosystem Restoration in Industry Clusters, Ministry of Education, South China University of Technology, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China
| | - Jianhua Cheng
- School of Environment and Energy, South China University of Technology, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China; The Key Lab of Pollution Control and Ecosystem Restoration in Industry Clusters, Ministry of Education, South China University of Technology, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China
| | - Xiaoqiang Zhu
- The Key Lab of Pollution Control and Ecosystem Restoration in Industry Clusters, Ministry of Education, South China University of Technology, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China; Guangzhou Pengkai Environment Technology Co., Ltd, Guangzhou 511493, PR China
| | - Guobin Wang
- Guangzhou Pengkai Environment Technology Co., Ltd, Guangzhou 511493, PR China
| | - Jieyun Xie
- Guangzhou Pengkai Environment Technology Co., Ltd, Guangzhou 511493, PR China
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Rabelo VWH, da Silva VD, Sanchez Nuñez ML, dos Santos Corrêa Amorim L, Buarque CD, Kuhn RJ, Abreu PA, Nunes de Palmer Paixão IC. Antiviral evaluation of 1,4-disubstituted-1,2,3-triazole derivatives against Chikungunya virus. Future Virol 2023; 18:865-880. [PMID: 37974899 PMCID: PMC10636642 DOI: 10.2217/fvl-2023-0142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 09/25/2023] [Indexed: 11/19/2023]
Abstract
Aim This work aimed to investigate the antiviral activity of two 1,4-disubstituted-1,2,3-triazole derivatives (1 and 2) against Chikungunya virus (CHIKV) replication. Materials & methods Cytotoxicity was analyzed using colorimetric assays and the antiviral potential was evaluated using plaque assays and computational tools. Results Compound 2 showed antiviral activity against CHIKV 181-25 in BHK-21 and Vero cells. Also, this compound presented a higher activity against CHIKV BRA/RJ/18 in Vero cells, like compound 1. Compound 2 exhibited virucidal activity and inhibited virus entry while compound 1 inhibited virus release. Molecular docking suggested that these derivatives inhibit nsP1 protein while compound 1 may also target capsid protein. Conclusion Both compounds exhibit promising antiviral activity against CHIKV by blocking different steps of virus replication.
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Affiliation(s)
- Vitor Won-Held Rabelo
- Programa de Pós-graduação em Ciências e Biotecnologia, Instituto de Biologia, Universidade Federal Fluminense, Niterói, RJ, CEP, 24210-201, Brazil
| | - Verônica Diniz da Silva
- Laboratório de Síntese Orgânica, Pontifícia Universidade Católica do Rio de Janeiro, Rio de Janeiro, RJ, CEP, 22451-900, Brazil
| | - Maria Leonisa Sanchez Nuñez
- Programa de Pós-graduação em Ciências e Biotecnologia, Instituto de Biologia, Universidade Federal Fluminense, Niterói, RJ, CEP, 24210-201, Brazil
| | - Leonardo dos Santos Corrêa Amorim
- Programa de Pós-graduação em Ciências e Biotecnologia, Instituto de Biologia, Universidade Federal Fluminense, Niterói, RJ, CEP, 24210-201, Brazil
- Gerência de Desenvolvimento Tecnológico, Instituto Vital Brazil, Niterói, RJ, 24230-410, Brazil
| | - Camilla Djenne Buarque
- Laboratório de Síntese Orgânica, Pontifícia Universidade Católica do Rio de Janeiro, Rio de Janeiro, RJ, CEP, 22451-900, Brazil
| | - Richard J Kuhn
- Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA
- Purdue Institute of Inflammation, Immunology, & Infectious Disease, Purdue University, West Lafayette, IN 47907, USA
| | - Paula Alvarez Abreu
- Instituto de Biodiversidade e Sustentabilidade (NUPEM), Universidade Federal do Rio de Janeiro, Macaé, RJ, CEP, 27965-045, Brazil
| | - Izabel Christina Nunes de Palmer Paixão
- Programa de Pós-graduação em Ciências e Biotecnologia, Instituto de Biologia, Universidade Federal Fluminense, Niterói, RJ, CEP, 24210-201, Brazil
- Departamento de Biologia Celular e Molecular, Instituto de Biologia, Universidade Federal Fluminense, Niterói, RJ, CEP, 24210-201, Brazil
- Programas de Pós-graduação em Biotecnologia Marinha e de Neurologia, Universidade Federal Fluminense, Niterói, RJ, Brazil
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Shan T, Li LY, Yang JM, Cheng Y. Role and clinical implication of autophagy in COVID-19. Virol J 2023; 20:125. [PMID: 37328875 PMCID: PMC10276507 DOI: 10.1186/s12985-023-02069-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 05/10/2023] [Indexed: 06/18/2023] Open
Abstract
The ongoing coronavirus disease 2019 (COVID-19) pandemic constitutes a serious public health concern worldwide. Currently, more than 6 million deaths have occurred despite drastic containment measures, and this number is still increasing. Currently, no standard therapies for COVID-19 are available, which necessitates identifying effective preventive and therapeutic agents against COVID-19. However, developing new drugs and vaccines is a time-consuming process, and therefore, repurposing the existing drugs or redeveloping related targets seems to be the best strategy to develop effective therapeutics against COVID-19. Autophagy, a multistep lysosomal degradation pathway contributing to nutrient recycling and metabolic adaptation, is involved in the initiation and progression of numerous diseases as a part of an immune response. The key role of autophagy in antiviral immunity has been extensively studied. Moreover, autophagy can directly eliminate intracellular microorganisms by selective autophagy, that is, "xenophagy." However, viruses have acquired diverse strategies to exploit autophagy for their infection and replication. This review aims to trigger the interest in the field of autophagy as an antiviral target for viral pathogens (with an emphasis on COVID-19). We base this hypothesis on summarizing the classification and structure of coronaviruses as well as the process of SARS-CoV-2 infection and replication; providing the common understanding of autophagy; reviewing interactions between the mechanisms of viral entry/replication and the autophagy pathways; and discussing the current state of clinical trials of autophagy-modifying drugs in the treatment of SARS-CoV-2 infection. We anticipate that this review will contribute to the rapid development of therapeutics and vaccines against COVID-19.
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Affiliation(s)
- Tianjiao Shan
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
- Hunan Provincial Engineering Research Centre of Translational Medicine and Innovative Drug, Changsha, 410011, China
| | - Lan-Ya Li
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
- Hunan Provincial Engineering Research Centre of Translational Medicine and Innovative Drug, Changsha, 410011, China
| | - Jin-Ming Yang
- Department of Toxicology and Cancer Biology, Department of Pharmacology, and Markey Cancer Center, University of Kentucky, Lexington, KY, 40536, USA.
| | - Yan Cheng
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
- Hunan Provincial Engineering Research Centre of Translational Medicine and Innovative Drug, Changsha, 410011, China.
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Li J, Fu C, Lin Q, Zeng T, Wang D, Huang X, Song S, Li C, Dong F. Fe(VI) activation system mediated by a solar-driven TiO 2 nanotubes electrode for CLQ degradation: Performances, mechanisms and pathways. JOURNAL OF HAZARDOUS MATERIALS 2023; 452:131274. [PMID: 36989796 DOI: 10.1016/j.jhazmat.2023.131274] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 03/21/2023] [Accepted: 03/21/2023] [Indexed: 06/19/2023]
Abstract
Ferrate (Fe(VI), FeO42-) has been widely used in the degradation of micropollutants with the advantages of high redox potential, no secondary pollution and inhibition of disinfection byproducts. However, the low transformation of Fe(V) and/or Fe(IV) by Fe(VI) and incomplete mineralization of pollutants limit their application. In this work, we designed a photo electric cell with TiO2 nanotubes (TNTs) and Pt serving as the anode and cathode to enhance the utilization of Fe(VI) (Fe(VI)-TNTs system). TNTs accelerated the generation of •OH via hVB+ oxidation of OH- and photogenerated electrons at Pt boosted the transformation of Fe(VI) to Fe(V) and/or Fe(IV), resulting in a 22.2 % enhancement of chloroquine (CLQ) removal compared to Fe(VI) alone. The results from EPR and quenching tests showed that Fe(VI), Fe(V), Fe(IV), •OH, O2•- and hVB+ coexisted in the Fe(VI)-TNTs system, among which Fe(V) and Fe(IV) were testified as the primary reactive substances accounting for 59 % of CLQ removal. The performance tests and recycling tests demonstrated that the Fe(VI)-TNTs system maintained excellent performance in an authentic water environment. The plausible degradation pathway of CLQ oxidized in the Fe(VI)-TNTs system was proposed with nine identified oxidation products via N-C cleavage, electrophilic addition and carboxylation processes. Based on the ECOSAR calculation, the constructed reaction system allowed a decrease in acute and chronic toxicity. Our findings provide a highly efficient and cost-effective strategy to enhance Fe(VI) application for micropollutant degradation in the future.
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Affiliation(s)
- Jinzhe Li
- College of Environment, Zhejiang University of Technology, Hangzhou 310014, China
| | - Chuyun Fu
- College of Environment, Zhejiang University of Technology, Hangzhou 310014, China
| | - Qiufeng Lin
- Department of Earth and Environmental Studies, Montclair State University, Montclair, NJ 07043, United States
| | - Tao Zeng
- College of Environment, Zhejiang University of Technology, Hangzhou 310014, China
| | - Da Wang
- College of Environment, Zhejiang University of Technology, Hangzhou 310014, China
| | - Xinwen Huang
- College of Environment, Zhejiang University of Technology, Hangzhou 310014, China
| | - Shuang Song
- College of Environment, Zhejiang University of Technology, Hangzhou 310014, China
| | - Cong Li
- School of Environment and Architecture, University of Shanghai for Science and Technology, Shanghai 200433, China
| | - Feilong Dong
- College of Environment, Zhejiang University of Technology, Hangzhou 310014, China; Shaoxing Research Institute, Zhejiang University of Technology, Shaoxing 312085, China.
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Rheingold SZ, Raval C, Gordon AM, Hardigan P. Zinc Supplementation Associated With a Decrease in Mortality in COVID-19 Patients: A Meta-Analysis. Cureus 2023; 15:e40231. [PMID: 37435275 PMCID: PMC10332820 DOI: 10.7759/cureus.40231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Accepted: 05/26/2023] [Indexed: 07/13/2023] Open
Abstract
The COVID-19 pandemic has had a significant impact on the world, resulting in millions of deaths worldwide and imposing economic, political, and social problems. The use of nutritional supplementation for the prevention and mitigation of COVID-19 remains controversial. This meta-analysis aims to investigate the association between zinc supplementation, mortality, and symptomatology, among COVID-19-infected patients. A meta-analysis was conducted to compare the outcomes of mortality and symptomology of patients with COVID-19 receiving zinc supplementation and those not receiving zinc supplementation. PubMed/Medline, Cochrane, Web of Science, and CINAHL Complete were independently searched with the search terms "zinc" AND "covid" OR "sars-cov-2" "COVID-19" OR "coronavirus". After duplicates were removed, 1215 articles were identified. Five of these studies were used to assess mortality outcomes, and two were used to assess symptomatology outcomes. The meta-analysis was conducted through R 4.2.1 software (R Foundation, Vienna, Austria). Heterogeneity was evaluated by calculating the I2 index. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. It was found that COVID-19-infected individuals treated with zinc supplements had a reduced risk of mortality compared with individuals not treated with a zinc supplement RR=0.63 (95%CI;0.52,0.77), p=0.005. For symptomology, it was found that COVID-19-infected individuals treated with zinc had no difference in symptomology than individuals not treated with a zinc supplement RR=0.52 (95%CI;0.00,24315.42), p=0.578. This data indicates that zinc supplementation is associated with decreased mortality in those with COVID-19 but does not change symptomatology. This is promising as zinc is widely available and may be valuable as a cost-effective way to prevent poor outcomes for those with COVID-19.
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Affiliation(s)
| | - Chirag Raval
- Research, Dr. Kiran C. Patel College of Allopathic Medicine, Davie, USA
| | | | - Patrick Hardigan
- Research, Dr. Kiran C. Patel College of Allopathic Medicine, Davie, USA
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Raghav PK, Mann Z, Ahluwalia SK, Rajalingam R. Potential treatments of COVID-19: Drug repurposing and therapeutic interventions. J Pharmacol Sci 2023; 152:1-21. [PMID: 37059487 PMCID: PMC9930377 DOI: 10.1016/j.jphs.2023.02.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 01/31/2023] [Accepted: 02/10/2023] [Indexed: 02/17/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection is caused when Spike-protein (S-protein) present on the surface of SARS-CoV-2 interacts with human cell surface receptor, Angiotensin-converting enzyme 2 (ACE2). This binding facilitates SARS-CoV-2 genome entry into the human cells, which in turn causes infection. Since the beginning of the pandemic, many different therapies have been developed to combat COVID-19, including treatment and prevention. This review is focused on the currently adapted and certain other potential therapies for COVID-19 treatment, which include drug repurposing, vaccines and drug-free therapies. The efficacy of various treatment options is constantly being tested through clinical trials and in vivo studies before they are made medically available to the public.
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Affiliation(s)
- Pawan Kumar Raghav
- Immunogenetics and Transplantation Laboratory, Department of Surgery, University of California San Francisco, San Francisco, CA, USA.
| | | | - Simran Kaur Ahluwalia
- Amity Institute of Biotechnology, Amity University, Sector-125, Noida, Uttar Pradesh, India
| | - Raja Rajalingam
- Immunogenetics and Transplantation Laboratory, Department of Surgery, University of California San Francisco, San Francisco, CA, USA
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35
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Mahdavi R, Talebpour Z. Analytical approaches for determination of COVID-19 candidate drugs in human biological matrices. Trends Analyt Chem 2023; 160:116964. [PMID: 36816451 PMCID: PMC9922681 DOI: 10.1016/j.trac.2023.116964] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 01/30/2023] [Accepted: 02/04/2023] [Indexed: 02/24/2023]
Abstract
Since the outbreak of the COVID-19 pandemic, the use of antiviral and other available drugs has been considered to combat or reduce the clinical symptoms of patients. In this regard, it would be necessary to choose sensitive and selective analytical techniques for pharmacokinetic and pharmacodynamic studies, monitoring of drug concentration in biological fluids, and determination of the most appropriate dose to achieve the desired effect on the disease. In the present study, the analytical techniques based on spectroscopy and chromatography with different detectors for diagnosis and determination of candidate drugs in the treatment of COVID-19 in human biological fluids are reviewed during the period 2015-2022. Moreover, various sample preparation and extraction techniques, are being used for this purpose, such as protein precipitation (PP), solid-phase extraction (SPE), liquid-liquid extraction (LLE), and QuEChERS (quick, easy, cheap, effective, rugged, and safe) are investigated.
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Affiliation(s)
- Rabee Mahdavi
- Department of Analytical Chemistry, Faculty of Chemistry, Alzahra University, Vanak, Tehran, Iran
| | - Zahra Talebpour
- Department of Analytical Chemistry, Faculty of Chemistry, Alzahra University, Vanak, Tehran, Iran,Analytical and Bioanalytical Research Centre, Alzahra University, Vanak, Tehran, Iran,Corresponding author. Department of Analytical Chemistry, Faculty of Chemistry, Alzahra University, Vanak, Tehran, Iran
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Corrêa BSG, de Barros S, Vaz JB, Peres MA, Uchiyama MK, da Silva AA, Furukawa LNS. COVID-19: Understanding the impact of anti-hypertensive drugs and hydroxychloroquine on the ACE1 and ACE2 in lung and adipose tissue in SHR and WKY rats. Physiol Rep 2023; 11:e15598. [PMID: 36750199 PMCID: PMC9904959 DOI: 10.14814/phy2.15598] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 01/16/2023] [Accepted: 01/18/2023] [Indexed: 02/09/2023] Open
Abstract
Hypertensive individuals taking anti-hypertensive drugs from renin-angiotensin system inhibitors may exhibit a more severe evolution of the disease when contracting the SARS-CoV-2 virus (COVID-19 disease) due to potential increases in ACE2 expression. The study investigated ACE1 and ACE2 axes and hydroxychloroquine in the lungs and adipose tissue of male and female normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHRs). SHRs were treated with losartan (10 mg/kg/day) or captopril (10 mg/kg/day) for 14 days or 7 days with hydroxychloroquine (200 mg/kg/day) in drinking water. WKY rats were also treated for 7 days with hydroxychloroquine. Blood pressure (BP), protein, and mRNA expression of ACE1 and ACE2 were analyzed in serum, adipose, and lung tissues. Losartan and captopril reduced BP in both sexes in SHR, whereas hydroxychloroquine increased BP in WKY rats. Losartan reduced ACE2 in serum and lungs in both sexes and in adipose tissue of male SHRs. Captopril decreased ACE2 protein in the lung of females and in adipose tissue in both sexes of SHRs. Hydroxychloroquine decreased ACE1 and ACE2 proteins in the lungs in both sexes and adipose tissue in male SHRs. In female WKY rats, ACE2 protein was lower only in the lungs and adipose tissue. Losartan effectively inhibited ACE2 in male and captopril in female SHRs. Hydroxychloroquine inhibited ACE2 in male SHRs and female WKY rats. These results further our understanding of the ACE2 mechanism in patients under renin-angiotensin anti-hypertensive therapy and in many trials using hydroxychloroquine for COVID-19 treatment and potential sex differences in response to drug treatment.
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Affiliation(s)
- Beatriz Santos Geoffroy Corrêa
- Laboratory of Renal Pathophysiology, Department of Internal Medicine, School of MedicineUniversity of São PauloSão PauloBrazil
| | - Silvana de Barros
- Hypertension Unit, Renal Division, General Hospital of School of MedicineUniversity of São PauloSão PauloBrazil
| | - Julia Braga Vaz
- Laboratory of Renal Pathophysiology, Department of Internal Medicine, School of MedicineUniversity of São PauloSão PauloBrazil
| | - Maria Angelica Peres
- Laboratory of Renal Pathophysiology, Department of Internal Medicine, School of MedicineUniversity of São PauloSão PauloBrazil
| | - Mayara Klimuk Uchiyama
- Laboratory of Supramolecular Chemistry & Nanotechnology, Department of Fundamental Chemistry, Institute of ChemistryUniversity of São PauloSão PauloBrazil
| | - Alexandre Alves da Silva
- Department of Physiology and BiophysicsUniversity of Mississippi Medical Center JacksonJacksonMississippiUSA
| | - Luzia Naoko Shinohara Furukawa
- Laboratory of Renal Pathophysiology, Department of Internal Medicine, School of MedicineUniversity of São PauloSão PauloBrazil
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A Clinical Insight on New Discovered Molecules and Repurposed Drugs for the Treatment of COVID-19. Vaccines (Basel) 2023; 11:vaccines11020332. [PMID: 36851211 PMCID: PMC9967525 DOI: 10.3390/vaccines11020332] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 01/28/2023] [Accepted: 01/30/2023] [Indexed: 02/05/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began churning out incredulous terror in December 2019. Within several months from its first detection in Wuhan, SARS-CoV-2 spread to the rest of the world through droplet infection, making it a pandemic situation and a healthcare emergency across the globe. The available treatment of COVID-19 was only symptomatic as the disease was new and no approved drug or vaccine was available. Another challenge with COVID-19 was the continuous mutation of the SARS-CoV-2 virus. Some repurposed drugs, such as hydroxychloroquine, chloroquine, and remdesivir, received emergency use authorization in various countries, but their clinical use is compromised with either severe and fatal adverse effects or nonavailability of sufficient clinical data. Molnupiravir was the first molecule approved for the treatment of COVID-19, followed by Paxlovid™, monoclonal antibodies (MAbs), and others. New molecules have variable therapeutic efficacy against different variants or strains of SARS-CoV-2, which require further investigations. The aim of this review is to provide in-depth information on new molecules and repurposed drugs with emphasis on their general description, mechanism of action (MOA), correlates of protection, dose and dosage form, route of administration, clinical trials, regulatory approval, and marketing authorizations.
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Abstract
The rapid spread of new pathogens (SARS-CoV-2 virus) that negatively affect the human body has huge consequences for the global public health system and the development of the global economy. Appropriate implementation of new safety regulations will improve the functioning of the current model supervising the inhibition of the spread of COVID-19 disease. Compliance with all these standards will have a key impact on the health behavior of individual social groups. There have been demonstrably effective treatments that proved to be effective but were rapidly dismissed for unknown reasons, such as ivermectin and hydroxychloroquine. Various measures are used in the world to help inhibit its development. The properties of this element provide hope in preventing the development of the SARS-CoV-2 virus. The aim of this review is to synthesize the latest literature data and to present the effect of sodium selenite in reducing the incidence of COVID-19 disease.
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Affiliation(s)
- Marek Kieliszek
- Department of Food Biotechnology and Microbiology, Institute of Food Sciences, Warsaw University of Life Sciences-SGGW, Nowoursynowska 159 C, 02-776, Warsaw, Poland.
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Prathima TS, Ahmad MG, Karuppasamy R, Chanda K, Balamurali MM. Investigation on Phyto‐active Constituent of
Clerodendrum paniculatum
as Therapeutic Agent against Viral Diseases. ChemistrySelect 2023. [DOI: 10.1002/slct.202203932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Affiliation(s)
- T. S. Prathima
- Division of Chemistry School of Advanced Sciences Vellore Institute of Technology Chennai Tamil Nadu India 600027
| | - Md. Gulzar Ahmad
- Department of Chemistry School of Advanced Sciences Vellore Institute of Technology Vellore Tamil Nadu India 632014
| | - Ramanathan Karuppasamy
- Department of Biotechnology School of BioSciences and Technology Vellore Institute of Technology Vellore Tamil Nadu India 632014
| | - Kaushik Chanda
- Department of Chemistry School of Advanced Sciences Vellore Institute of Technology Vellore Tamil Nadu India 632014
| | - M. M. Balamurali
- Division of Chemistry School of Advanced Sciences Vellore Institute of Technology Chennai Tamil Nadu India 600027
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Nag A, Dasgupta A, Sengupta S, Lai TK, Acharya K. An in-silico pharmacophore-based molecular docking study to evaluate the inhibitory potentials of novel fungal triterpenoid Astrakurkurone analogues against a hypothetical mutated main protease of SARS-CoV-2 virus. Comput Biol Med 2023; 152:106433. [PMID: 36565483 PMCID: PMC9767885 DOI: 10.1016/j.compbiomed.2022.106433] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Revised: 11/21/2022] [Accepted: 12/13/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND The main protease is an important structural protein of SARS-CoV-2, essential for its survivability inside a human host. Considering current vaccines' limitations and the absence of approved therapeutic targets, Mpro may be regarded as the potential candidate drug target. Novel fungal phytocompound Astrakurkurone may be studied as the potential Mpro inhibitor, considering its medicinal properties reported elsewhere. METHODS In silico molecular docking was performed with Astrakurkurone and its twenty pharmacophore-based analogues against the native Mpro protein. A hypothetical Mpro was also constructed with seven mutations and targeted by Astrakurkurone and its analogues. Furthermore, multiple parameters such as statistical analysis (Principal Component Analysis), pharmacophore alignment, and drug likeness evaluation were performed to understand the mechanism of protein-ligand molecular interaction. Finally, molecular dynamic simulation was done for the top-ranking ligands to validate the result. RESULT We identified twenty Astrakurkurone analogues through pharmacophore screening methodology. Among these twenty compounds, two analogues namely, ZINC89341287 and ZINC12128321 showed the highest inhibitory potentials against native and our hypothetical mutant Mpro, respectively (-7.7 and -7.3 kcal mol-1) when compared with the control drug Telaprevir (-5.9 and -6.0 kcal mol-1). Finally, we observed that functional groups of ligands namely two aromatic and one acceptor groups were responsible for the residual interaction with the target proteins. The molecular dynamic simulation further revealed that these compounds could make a stable complex with their respective protein targets in the near-native physiological condition. CONCLUSION To conclude, Astrakurkurone analogues ZINC89341287 and ZINC12128321 can be potential therapeutic agents against the highly infectious SARS-CoV-2 virus.
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Affiliation(s)
- Anish Nag
- Department of Life Sciences, CHRIST (Deemed to be University), Bangalore, Karnataka, India
| | - Adhiraj Dasgupta
- Department of Botany, University of Calcutta, Kolkata, West Bengal, India
| | - Sutirtha Sengupta
- Department of Life Sciences, CHRIST (Deemed to be University), Bangalore, Karnataka, India
| | - Tapan Kumar Lai
- Department of Chemistry, Vidyasagar Metropolitan College, Kolkata, West Bengal, India
| | - Krishnendu Acharya
- Department of Botany, University of Calcutta, Kolkata, West Bengal, India.
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Aleebrahim-Dehkordi E, Soveyzi F, Saberianpour S, Rafieian-Kopaei M. Are Herbal-peptides Effective as Adjunctive Therapy in Coronavirus Disease COVID-19? Curr Drug Res Rev 2023; 15:29-34. [PMID: 36029074 DOI: 10.2174/2589977514666220826155013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 02/16/2022] [Accepted: 02/16/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Plant antiviral peptides (AVP) are macromolecules that can inhibit the pathogenesis of viruses by affecting their pathogenic mechanism, but most of these peptides can bind to cell membranes, inhibit viral receptors, and prevent viruses. Recently, due to the coronavirus pandemic, the availability of appropriate drugs with low side effects is needed. In this article, the importance of plant peptides in viral inhibition, especially viral inhibition of the coronavirus family, will be discussed. METHODS By searching the databases of PubMed, Scopus, Web of Science, the latest articles on plant peptides effective on the COVID-19 virus were collected and reviewed. RESULTS Some proteins can act against the COVID-19 virus by blocking sensitive receptors in COVID-19, such as angiotensin-converting enzyme 2 (ACE2). The 23bp sequence of the ACE2 alpha receptor chain can be considered as a target for therapeutic peptides. Protease and RNAP inhibitors and other important receptors that are active against COVID-19 should also be considered. CONCLUSION Herbal medicines with AVP, especially those with a long history of antiviral effects, might be a good choice in complement therapy against the COVID-19 virus.
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Affiliation(s)
- Elahe Aleebrahim-Dehkordi
- Systematic Review and Meta-Analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
- Nutritional Health Team (NHT), Universal Scientific Education and Research Network (USERN), Tehran, Iran
- Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Faezeh Soveyzi
- Systematic Review and Meta-Analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
- Department of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Shirin Saberianpour
- Department of Molecular Medicine, Vascular and Endovascular Surgery Research Center, Mashhad University of Medical Science, Mashhad, Iran
| | - Mahmoud Rafieian-Kopaei
- Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
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Kumar A, Sharma A, Tirpude NV, Thakur S, Kumar S. Combating the Progression of Novel Coronavirus SARS-CoV-2 Infectious Disease: Current State and Future Prospects in Molecular Diagnostics and Drug Discovery. Curr Mol Med 2023; 23:127-146. [PMID: 34344288 DOI: 10.2174/1566524021666210803154250] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 04/07/2021] [Accepted: 04/14/2021] [Indexed: 12/16/2022]
Abstract
A highly infectious and life-threatening virus was first reported in Wuhan, China, in late 2019, and it rapidly spread all over the world. This novel virus belongs to the coronavirus family and is associated with severe acute respiratory syndrome (SARS), causing respiratory disease known as COVID-19. In March 2020, WHO has declared the COVID-19 outbreak a global pandemic. Its morbidity and mortality rates are swiftly rising day by day, with the situation becoming more severe and fatal for the comorbid population. Many COVID-19 patients are asymptomatic, but they silently spread the infection. There is a need for proper screening of infected patients to prevent the epidemic transmission of disease and for early curative interventions to reduce the risk of developing severe complications from COVID-19. To date, the diagnostic assays are of two categories, molecular detection of viral genetic material by real-time RTpolymerase chain reaction and serological test, which relies on detecting antiviral antibodies. Unfortunately, there are no effective prophylactics and therapeutics available against COVID-19. However, a few drugs have shown promising antiviral activity against it, and these presently are being referred for clinical trials, albeit FDA has issued an Emergency Use Authorization (EUA) for the emergency use of a few drugs for SARSCoV- 2 infection. This review provides an insight into current progress, challenges and future prospects of laboratory detection methods of COVID-19, and highlights the clinical stage of the major evidence-based drugs/vaccines recommended against the novel SARS-CoV-2 pandemic virus.
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Affiliation(s)
- Arbind Kumar
- COVID-19 Testing Facility, CSIR-Institute of Himalayan Bioresource& Technology (IHBT), Palampur, India
| | - Aashish Sharma
- COVID-19 Testing Facility, CSIR-Institute of Himalayan Bioresource& Technology (IHBT), Palampur, India
| | - Narendra Vijay Tirpude
- COVID-19 Testing Facility, CSIR-Institute of Himalayan Bioresource& Technology (IHBT), Palampur, India
| | - Sharad Thakur
- COVID-19 Testing Facility, CSIR-Institute of Himalayan Bioresource& Technology (IHBT), Palampur, India
| | - Sanjay Kumar
- COVID-19 Testing Facility, CSIR-Institute of Himalayan Bioresource& Technology (IHBT), Palampur, India
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43
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Strojil J, Suchánková H. Lessons for teaching from the pandemic. Br J Clin Pharmacol 2023; 89:43-45. [PMID: 32839969 DOI: 10.1111/bcp.14529] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 08/10/2020] [Accepted: 08/18/2020] [Indexed: 01/20/2023] Open
Affiliation(s)
- Jan Strojil
- Department of Pharmacology, Faculty of Medicine and Dentistry, Palacký University Olomouc, Olomouc, Czech Republic
| | - Hana Suchánková
- Department of Pharmacology, Faculty of Medicine and Dentistry, Palacký University Olomouc, Olomouc, Czech Republic
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44
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Verma R, Raj S, Berry U, Ranjith-Kumar CT, Surjit M. Drug Repurposing for COVID-19 Therapy: Pipeline, Current Status and Challenges. DRUG REPURPOSING FOR EMERGING INFECTIOUS DISEASES AND CANCER 2023:451-478. [DOI: 10.1007/978-981-19-5399-6_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Sharma S, Sharma A, Bhattacharyya D, Chauhan RS. Computational identification of potential inhibitory compounds in Indian medicinal and aromatic plant species against major pathogenicity determinants of SARS-CoV-2. J Biomol Struct Dyn 2022; 40:14096-14114. [PMID: 34766880 DOI: 10.1080/07391102.2021.2000500] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
SARS-CoV-2 (COVID-19) viral pandemic has been reported across 223 countries and territories. Globalized vaccination programs alongside administration of repurposed drugs will assumingly confer a stronger and longer individual specific immune protection. However, considering possible recurrence of the disease via new variants, a conveniently deliverable phytopharmaceutical drug might be the best option for COVID-19 treatment. In the current study, the efforts have been made to identify potential leads for inhalation therapy as nasal swabs have been reported to transfer viral load prominently. In that direction, 2363 Essential oil (EOs) compounds from Indian medicinal and aromatic plants were screened through docking analysis and potential candidates were shortlisted that can interfere with viral pathogenicity. The main protease (Mpro) of SARS-CoV-2 interacted closely with jatamansin (JM), 6,7-dehydroferruginol (FG) and beta-sitosterol (BS), while Papain-like Protease (PLpro) with friedelane-3-one (F3O) and lantadene D (LD) independently. Reduced Lantadene A (LAR) exhibited preferable interaction with RNA-dependent-RNA-polymerase (RdRp) whereas Lantadene A (LA) with RdRp and spike-glycoprotein (SG-pro) both target proteins. When compared against highest binding affinity conformations of well-known inhibitors of targets, these prioritized compounds conferred superior or comparable SARS-CoV-2 protein inhibition. Additionally, promising results were noted from pharmacokinetics prediction for all shortlisted compounds. Besides, molecular dynamics simulation for 100 ns in two replicates and binding free energy analysis revealed the stability of complexes with optimum compactness. To the best of our knowledge, the current investigation is a unique initial attempt whereby EO compounds have been computationally screened, irrespective of their known medicinal properties to fight COVID-19 infection.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Shilpa Sharma
- Department of Biotechnology, School of Engineering & Applied Sciences, Bennett University, Uttar Pradesh, India
| | - Ashish Sharma
- Department of Biotechnology, School of Engineering & Applied Sciences, Bennett University, Uttar Pradesh, India
| | - Dipto Bhattacharyya
- Department of Biotechnology, School of Engineering & Applied Sciences, Bennett University, Uttar Pradesh, India
| | - Rajinder S Chauhan
- Department of Biotechnology, School of Engineering & Applied Sciences, Bennett University, Uttar Pradesh, India
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Khattab ESAEH, Ragab A, Abol-Ftouh MA, Elhenawy AA. Therapeutic strategies for Covid-19 based on molecular docking and dynamic studies to the ACE-2 receptors, Furin, and viral spike proteins. J Biomol Struct Dyn 2022; 40:13291-13309. [PMID: 34647855 PMCID: PMC8544674 DOI: 10.1080/07391102.2021.1989036] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
SARS-CoV-2 is a pandemic virus that caused infections and deaths in many world countries, including the Middle East. The virus-infected human cells by binding via ACE-2 receptor through the Spike protein of the virus with Furin's help causing cell membrane fusion leading to Covid-19-cell entry. No registered drugs or vaccines are triggering this pandemic viral disease yet. Our present work is based on molecular docking and dynamics simulation that performed to spike protein-ACE-2 interface complex, ACE-2 receptor, Spike protein (RBD), and Furin as targets for new small molecules. These drugs target new potential therapies to show their probabilities toward the active sites of mentioned proteins, strongly causing inhibition and/or potential therapy for covid-19. All target proteins were estimated against new target compounds under clinical trials and repurposing drugs currently present. Possibilities of those molecules and potential therapeutics acting on a certain target were predicted. MD simulations over 200 ns with molecular mechanics-generalized Born surface area (MMGBSA) binding energy calculations were performed. The structural and energetic analyses demonstrated the stability of the ligands-MPros complex. Our present work will introduce new visions of some biologically active molecules for further studies in-vitro and in-vivo for Covid-19, repurposing of these molecules should be taking place under clinical works and offering different strategies for drugs repurposing against Covid-19 diseases.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
| | - Ahmed Ragab
- Department of Chemistry, Faculty of Science (Boys), Al-Azhar University, Nasr City, Cairo, Egypt,CONTACT Ahmed Ragab ; Department of Chemistry, Faculty of Science (Boys), Al-Azhar University, Nasr City, Cairo11884, Egypt
| | - Mahmoud A. Abol-Ftouh
- Department of Chemistry, Faculty of Science (Boys), Al-Azhar University, Nasr City, Cairo, Egypt,Mahmoud A. Abol-Ftouh Department of Chemistry, Faculty of Science (Boys), Al-Azhar University, Nasr City, Cairo11884, Egypt
| | - Ahmed A. Elhenawy
- Department of Chemistry, Faculty of Science (Boys), Al-Azhar University, Nasr City, Cairo, Egypt
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47
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Prasanth DSNBK, Murahari M, Chandramohan V, Guntupalli C, Atmakuri LR. Computational study for identifying promising therapeutic agents of hydroxychloroquine analogues against SARS-CoV-2. J Biomol Struct Dyn 2022; 40:11822-11836. [PMID: 34396938 DOI: 10.1080/07391102.2021.1965027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Hydroxychloroquine (HCQ) and its derivatives have recently gained tremendous attention as a probable medicinal agent in the COVID-19 outbreak caused by SARS-CoV-2. An efficient agent to act directly in inhibiting the SARS-CoV-2 replication is yet to be achieved. Thus, the goal is to investigate the dynamic nature of HCQ derivatives against SARS-CoV-2 main protease and spike proteins. Molecular docking studies were also performed to understand their binding affinity in silico methods using the vital protein domains and enzymes involved in replicating and multiplying SARS-CoV-2, which were the main protease and spike protein. Molecular Dynamic simulations integrated with MM-PBSA calculations have identified In silico potential inhibitors ZINC05135012 and ZINC59378113 against the main protease with -185.171 ± 16.388, -130.759 ± 15.741 kJ/mol respectively, ZINC16638693 and ZINC59378113 against spike protein -141.425 ± 22.447, -129.149 ± 11.449 kJ/mol. Identified Hit molecules had demonstrated Drug Likeliness features, PASS values and ADMET predictions with no violations. Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- D S N B K Prasanth
- Pharmacognosy Research Division, K L College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, India
| | - Manikanta Murahari
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, Bangalore, India
| | - Vivek Chandramohan
- Department of Biotechnology, Siddaganga Institute of Technology, Tumakuru, India
| | - Chakravarthi Guntupalli
- Pharmacognosy Research Division, K L College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, India
| | - Lakshmana Rao Atmakuri
- Department of Pharmaceutical Analysis, V. V. Institute of Pharmaceutical Sciences, Gudlavalleru, India
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Trivedi A, Ahmad R, Siddiqui S, Misra A, Khan MA, Srivastava A, Ahamad T, Khan MF, Siddiqi Z, Afrin G, Gupta A, Upadhyay S, Husain I, Ahmad B, Mehrotra S, Kant S. Prophylactic and therapeutic potential of selected immunomodulatory agents from Ayurveda against coronaviruses amidst the current formidable scenario: an in silico analysis. J Biomol Struct Dyn 2022; 40:9648-9700. [PMID: 34243689 DOI: 10.1080/07391102.2021.1932601] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
There is currently a dearth of specific therapies to treat respiratory infections caused by the three related species of coronaviruses viz. SARS-CoV-2, SARS-CoV and MERS-CoV. Prevention from disease is currently the safest and most convenient alternative available. The present study aimed to evaluate the preventive and therapeutic effect of fifteen phytoconstituents from medicinal plants of Ayurveda against coronaviruses by in silico screening. All the phytoconstituents exhibited rapid GI absorption and bioavailability and most of them had no toxicity versus reference drug chloroquine. BAS analyses revealed that most of the phytocomponents had favorable bioactivity scores towards biological target proteins. Principal component analysis revealed that most of the phytoconstituents fell close to chloroquine in 3D projection of chemical space. Affinity of phytoconstituents towards SARS-CoV-2 spike protein-human ACE2 complex decreased as isomeldenin > tinosporaside > EGCG whereas in case of unbound ACE2, the strength of binding followed the order isomeldenin > tinosporaside > ellagic acid. Towards SARS-CoV-2 main and papain-like proteases, the affinity decreased as isomeldenin > EGCG > tinosporaside and EGCG > tinosporaside > isomeldenin, respectively. Most phytoconstituents displayed significant binding kinetics to the selected protein targets than chloroquine. SAR analysis revealed that isomeldenin, tinosporaside, EGCG and ellagic acid bind to viral spike glycoproteins via H-bond, Pi-Pi, Pi-sigma and Pi-alkyl type interactions. Molecular dynamics simulation of isomeldenin and EGCG with SARS-CoV and SARS-CoV-2 spike glycoproteins exhibited low deviations throughout the 100 ns simulation indicating good stability and compactness of the protein-ligand complexes. Thus, the above four phytoconstituents have the potential to emerge as prophylactic and therapeutic agents against coronaviruses if investigated further in vitro and in vivo.
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Affiliation(s)
- Anchal Trivedi
- Department of Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | - Rumana Ahmad
- Department of Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | - Sahabjada Siddiqui
- Department of Biotechnology, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | - Aparna Misra
- Department of Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | | | - Aditi Srivastava
- Department of Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | - Tanveer Ahamad
- Department of Biotechnology, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | - Mohd Faheem Khan
- Department of Biotechnology, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | - Zeba Siddiqi
- Department of Medicine, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | - Gazala Afrin
- Department of Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | - Anamika Gupta
- Department of Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | - Shivbrat Upadhyay
- Department of Biotechnology, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | - Ishrat Husain
- Department of Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | - Bilal Ahmad
- Research Cell, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | - Sudhir Mehrotra
- Department of Biochemistry, University of Lucknow, Lucknow, Uttar Pradesh, India
| | - Surya Kant
- Department of Respiratory Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
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de Moraes VY, Marra AR, Matos LL, Serpa A, Rizzo LV, Cendoroglo M, Lenza M. Hydroxychloroquine for treatment of COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials. EINSTEIN-SAO PAULO 2022; 20:eRW0045. [PMID: 36477526 PMCID: PMC9744433 DOI: 10.31744/einstein_journal/2022rw0045] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 08/30/2022] [Indexed: 11/23/2022] Open
Abstract
OBJECTIVE We performed a systematic review of the literature and meta-analysis on the efficacy and safety of hydroxychloroquine to treat COVID-19 patients. METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and LILACS (January 2019 to March 2021) for patients aged 18 years or older, who had COVID-19 and were treated with hydroxychloroquine versus placebo or standard of care. We also searched the WHO Clinical Trials Registry for ongoing and recently completed studies, and the reference lists of selected articles and reviews for possible relevant studies, with no restrictions regarding language or publication status. Random-effects models were used to obtain pooled mean differences of treatment effect on mortality, and serious adverse effects between hydroxychloroquine and the Control Group (standard of care or placebo); heterogeneity was assessed using the I2 and the Cochran´s Q statistic. RESULTS Nine studies met the inclusion criteria and were included in the meta-analysis. There was no significant difference in mortality rate between patients treated with hydroxychloroquine compared to standard of care or placebo (16.7% versus 18.5%; pooled risk ratio 1.09; 95% confidence interval: 0.99-1.19). Also, the rate of serious adverse effects was similar between both Groups, Hydroxychloroquine and Control (3.7% versus 2.9%; pooled risk ratio 1.22; 95% confidence interval: 0.76-1.96). CONCLUSION Hydroxychloroquine is not efficacious in reducing mortality of COVID-19 patients. PROSPERO DATABASE REGISTRATION (www.crd.york.ac.uk/prospero) under number CRD42020197070.
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Affiliation(s)
- Vinícius Ynoe de Moraes
- Hospital Israelita Albert EinsteinSão PauloSPBrazilHospital Israelita Albert Einstein, São Paulo, SP, Brazil.
| | - Alexandre Rodrigues Marra
- Hospital Israelita Albert EinsteinSão PauloSPBrazilHospital Israelita Albert Einstein, São Paulo, SP, Brazil.
| | - Leandro Luongo Matos
- Hospital Israelita Albert EinsteinSão PauloSPBrazilHospital Israelita Albert Einstein, São Paulo, SP, Brazil.
| | - Ary Serpa
- Hospital Israelita Albert EinsteinSão PauloSPBrazilHospital Israelita Albert Einstein, São Paulo, SP, Brazil.
| | - Luiz Vicente Rizzo
- Hospital Israelita Albert EinsteinSão PauloSPBrazilHospital Israelita Albert Einstein, São Paulo, SP, Brazil.
| | - Miguel Cendoroglo
- Hospital Israelita Albert EinsteinSão PauloSPBrazilHospital Israelita Albert Einstein, São Paulo, SP, Brazil.
| | - Mario Lenza
- Hospital Israelita Albert EinsteinSão PauloSPBrazilHospital Israelita Albert Einstein, São Paulo, SP, Brazil.
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50
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Sharun K, Tiwari R, Yatoo MI, Natesan S, Megawati D, Singh KP, Michalak I, Dhama K. A comprehensive review on pharmacologic agents, immunotherapies and supportive therapeutics for COVID-19. NARRA J 2022; 2:e92. [PMID: 38449903 PMCID: PMC10914132 DOI: 10.52225/narra.v2i3.92] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 12/06/2022] [Indexed: 03/08/2024]
Abstract
The emergence of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected many countries throughout the world. As urgency is a necessity, most efforts have focused on identifying small molecule drugs that can be repurposed for use as anti-SARS-CoV-2 agents. Although several drug candidates have been identified using in silico method and in vitro studies, most of these drugs require the support of in vivo data before they can be considered for clinical trials. Several drugs are considered promising therapeutic agents for COVID-19. In addition to the direct-acting antiviral drugs, supportive therapies including traditional Chinese medicine, immunotherapies, immunomodulators, and nutritional therapy could contribute a major role in treating COVID-19 patients. Some of these drugs have already been included in the treatment guidelines, recommendations, and standard operating procedures. In this article, we comprehensively review the approved and potential therapeutic drugs, immune cells-based therapies, immunomodulatory agents/drugs, herbs and plant metabolites, nutritional and dietary for COVID-19.
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Affiliation(s)
- Khan Sharun
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, India
| | - Ruchi Tiwari
- Department of Veterinary Microbiology and Immunology, College of Veterinary Sciences, UP Pandit Deen Dayal Upadhayay Pashu Chikitsa Vigyan Vishwavidyalay Evum Go-Anusandhan Sansthan (DUVASU), Mathura, India
| | - Mohd I. Yatoo
- Division of Veterinary Clinical Complex, Faculty of Veterinary Sciences and Animal Husbandry, Shuhama, Alusteng Srinagar, Sher-E-Kashmir University of Agricultural Sciences and Technology of Kashmir, Shalimar, Jammu and Kashmir, India
| | - Senthilkumar Natesan
- Department of Infectious Diseases, Indian Institute of Public Health Gandhinagar, Opp to Airforce station HQ, Gandhinagar, India
| | - Dewi Megawati
- Department of Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Warmadewa University, Denpasar, Indonesia
- Department of Medical Microbiology and Immunology, University of California, Davis, California, USA
| | - Karam P. Singh
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, India
| | - Izabela Michalak
- Faculty of Chemistry, Department of Advanced Material Technologies, Wrocław University of Science and Technology, Wrocław, Poland
| | - Kuldeep Dhama
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, India
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