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Abedi Dorcheh F, Balmeh N, Hejazi SH, Allahyari Fard N. Investigation of the mutated antimicrobial peptides to inhibit ACE2, TMPRSS2 and GRP78 receptors of SARS-CoV-2 and angiotensin II type 1 receptor (AT1R) as well as controlling COVID-19 disease. J Biomol Struct Dyn 2025; 43:1641-1664. [PMID: 38109185 DOI: 10.1080/07391102.2023.2292307] [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: 12/08/2022] [Accepted: 11/23/2023] [Indexed: 12/19/2023]
Abstract
SARS-CoV-2 is a global problem nowadays. Based on studies, some human receptors are involved in binding to SARS-CoV-2. Thus, the inhibition of these receptors can be effective in the treatment of Covid-19. Because of the proven benefits of antimicrobial peptides (AMPs) and the side effects of chemical drugs, they can be known as an alternative to recent medicines. RCSB PDB to obtain PDB id, StraPep and PhytAMP to acquire Bio-AMPs information and 3-D structure, and AlgPred, Toxinpred, TargetAntiAngio, IL-4pred, IL-6pred, ACPred and Hemopred databases were used to find the best score peptide features. HADDOCK 2.2 was used for molecular docking analysis, and UCSF Chimera software version 1.15, SWISS-MODEL and BIOVIA Discovery Studio Visualizer4.5 were used for mutation and structure modeling. Furthermore, MD simulation results were achieved from GROMACS 4.6.5. Based on the obtained results, the Moricin peptide was found to have the best affinity for ACE2. Moreover, Bacteriocin leucocin-A had the highest affinity for GRP78, Cathelicidin-6 had the best affinity for AT1R, and Bacteriocin PlnK had the best binding affinity for TMPRSS2. Additionally, Bacteriocin glycocin F, Bacteriocin lactococcin-G subunit beta and Cathelicidin-6 peptides were the most common compounds among the four receptors. However, these peptides also have some side effects. Consequently, the mutation eliminated the side effects, and MD simulation results indicated that the mutation proved the result of the docking analysis. The effect of AMPs on ACE2, GRP78, TMPRSS2 and AT1R receptors can be a novel treatment for Covid-19.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Fatemeh Abedi Dorcheh
- Department of Biotechnology, School of Bioscience and Biotechnology, Shahid Ashrafi Esfahani University of Isfahan, Sepahan Shahr, Iran
| | - Negar Balmeh
- Skin Diseases and Leishmaniasis Research Center, Department of Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Seyed Hossein Hejazi
- Skin Diseases and Leishmaniasis Research Center, Department of Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Najaf Allahyari Fard
- Department of Systems Biotechnology, National Institute of Genetic Engineering & Biotechnology (NIGEB), Tehran, Iran
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Rath SK, Dash AK, Sarkar N, Panchpuri M. A Glimpse for the subsistence from pandemic SARS-CoV-2 infection. Bioorg Chem 2025; 154:107977. [PMID: 39603070 DOI: 10.1016/j.bioorg.2024.107977] [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: 09/22/2024] [Revised: 11/13/2024] [Accepted: 11/15/2024] [Indexed: 11/29/2024]
Abstract
COVID-19 is an emerging viral pandemic caused by SARS-CoV-2, which is the causative agent of unprecedented disease-causing public health threats globally. Worldwide, this outbreak is wreaking havoc due to failure in risk assessment regarding the urgency of the pandemic. As per the reports, many secondary complications which include neurological, nephrological, gastrointestinal, cardiovascular, immune, and hepatic abnormalities, are linked with COVID -19 infection which is associated with prominent respiratory disorders including pneumonia. Hindering the initial binding of the virus with Angiotensin-converting enzyme 2 (ACE2) through the spike protein is one potential boulevard of monoclonal antibodies. Although some drug regimens and vaccines have shown safety in trials, none have been entirely successful yet. This review highlights, some of the potential antibodies (tocilizumab, Sarilumab, Avdoralimab, Lenzilumab, Interferon (alfa /beta /gamma)) screened against SARS-CoV-2 and the most promising drugs (Favipiravir, Hydroxychloroquine, Niclosamide, Ribavirin, Baricitinib, Remdesivir, Arbidol Losartan, Ritonavir, Lopinavir, Baloxavir, Nitazoxanide, Camostat) in various stages of development with their synthetic protocol and their clinical projects are discussed to counter COVID -19.
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Affiliation(s)
- Santosh K Rath
- School of Pharmaceuticals and Population Health Informatics, Faculty of Pharmacy, DIT University, Dehradun, Uttarakhand, 248009, India.
| | | | - Nandan Sarkar
- Department of Pharmaceutical Technology, School of Health and Medical Sciences, Adamas University, Barasat, Kolkata 700126, India
| | - Mitali Panchpuri
- School of Pharmaceuticals and Population Health Informatics, Faculty of Pharmacy, DIT University, Dehradun, Uttarakhand, 248009, India
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Nasir A, Yabalak E. Exploring natural herbs: their role in treating male infertility, enhancing sexual desire and addressing urological disorders. INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH 2024:1-27. [PMID: 39360362 DOI: 10.1080/09603123.2024.2408417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 09/18/2024] [Indexed: 10/04/2024]
Abstract
Infertility affects 8-12% of couples globally, with male factors contributing to around 40% of cases. Common male infertility issues include erectile dysfunction (ED) and low sperm count or quality, which account for over 90% of cases. These problems often result from anatomical, hormonal, or genetic abnormalities. This review focuses on natural aphrodisiac herbs commonly used to address ED, providing detailed information on their botanical characteristics, metabolic pathways, recommended dosages, phytochemical properties, side effects, origins, and traditional uses. It also reviews recent studies on medicinal herbs that boost sexual desire and treat urological conditions. By compiling reliable findings from the past decade, the study aims to serve as a comprehensive resource for individuals dealing with sexual health issues. Through careful evaluation of each herb, it offers insights into their effectiveness and limitations, emphasizing the potential of natural treatments as complementary alternatives to conventional therapies for male infertility and related conditions.
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Affiliation(s)
- Abir Nasir
- Faculty of Science, Department of Chemistry, Mersin University, Mersin, Turkey
| | - Erdal Yabalak
- Department of Nanotechnology and Advanced Materials, Mersin University, Mersin, Turkey
- Department of Chemistry and Chemical Processing Technologies, Technical Science Vocational School, Mersin University, Mersin, Turkey
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Sadowski J, Klaudel T, Rombel-Bryzek A, Bułdak RJ. Cognitive dysfunctions in the course of SARS‑CoV‑2 virus infection, including NeuroCOVID, frontal syndrome and cytokine storm (Review). Biomed Rep 2024; 21:103. [PMID: 38800038 PMCID: PMC11117100 DOI: 10.3892/br.2024.1791] [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: 12/11/2023] [Accepted: 04/05/2024] [Indexed: 05/29/2024] Open
Abstract
During the coronavirus disease 2019 (COVID-19) pandemic, cognitive impairment of varying degrees of severity began to be observed in a significant percentage of patients. The present study discussed the impact of immunological processes on structural and functional changes in the central nervous system and the related cognitive disorders. The purpose of the present review was to analyse and discuss available information from the scientific literature considering the possible relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection and cognitive impairment, including NeuroCOVID, frontal syndrome and cytokine storm. A systematic literature review was conducted using: Google Scholar, Elsevier and the PubMed database. When searching for materials, the following keywords were used: 'cognitive dysfunctions', 'SARS-CoV-2', 'COVID-19', 'Neuro-SARS2', 'NeuroCOVID', 'frontal syndrome', 'cytokine storm', 'Long COVID-19'. A total of 96 articles were included in the study. The analysis focused on the characteristics of each study's materials, methods, results and conclusions. SARS-CoV-2 infection may induce or influence existing cognitive disorders of various nature and severity. The influence of immunological factors related to the response against SARS-CoV-2 on the disturbance of cerebral perfusion, the functioning of nerve cells and the neuroprotective effect has been demonstrated. Particular importance is attached to the cytokine storm and the related difference between pro- and anti-inflammatory effects, oxidative stress, disturbances in the regulation of the hypothalamic-pituitary-adrenal axis and the stress response of the body.
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Affiliation(s)
- Jakub Sadowski
- Student Scientific Society of Clinical Biochemistry and Regenerative Medicine, Department of Clinical Biochemistry and Laboratory Diagnostics, Institute of Medical Sciences, University of Opole, 45-050 Opole, Poland
| | - Tomasz Klaudel
- Student Scientific Society of Clinical Biochemistry and Regenerative Medicine, Department of Clinical Biochemistry and Laboratory Diagnostics, Institute of Medical Sciences, University of Opole, 45-050 Opole, Poland
| | - Agnieszka Rombel-Bryzek
- Department of Clinical Biochemistry and Laboratory Diagnostics, Institute of Medical Sciences, University of Opole, 45-050 Opole, Poland
| | - Rafał Jakub Bułdak
- Department of Clinical Biochemistry and Laboratory Diagnostics, Institute of Medical Sciences, University of Opole, 45-050 Opole, Poland
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O'Regan R, Harnedy F, Reynolds B, Cormican L. Ethnic disparities and COVID-19 pneumonia in Ireland: a single-centre descriptive study of hospitalised patients in a tertiary university teaching hospital. Ir J Med Sci 2024; 193:1131-1136. [PMID: 38231319 PMCID: PMC11128384 DOI: 10.1007/s11845-023-03597-y] [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: 03/27/2023] [Accepted: 12/06/2023] [Indexed: 01/18/2024]
Abstract
In this study, we aim to describe the demographic, clinical and imaging characteristics, treatment course and subsequent outcomes of the first 116 cases presenting to a tertiary Dublin hospital with COVID-19 infection and to compare whether ethnic minority background was a risk factor for poorer disease outcomes in this cohort. Of 116 cases analysed, 100 (86%) patients presented from the community, 6 (5%) from care homes and 10 (9%) were existing inpatients. Fifty-four (46%) patients identified as being from an ethnic minority group. One hundred fourteen (98%) patients reported two or more symptoms at time of diagnosis with 81 (70%) patients having confirmed radiological findings of COVID-19 infection. Median duration of symptoms prior to hospital presentation was 6 days (IQR 3-10 days). The median age at presentation was 52 years (IQR 43-65). Co-morbidities recorded included hypertension, hyperlipidaemia, type 2 diabetes mellitus, underlying respiratory disease, previous or current malignancy and current smoker. Twenty-six patients (22%) required ICU admission, 20 (76.9%) of these were from all other ethnic groups combined and 6 (10%) from White Irish group. Adjusting for variables of age, ethnicity and gender, all other ethnic groups combined were five times more likely to require ICU admission than White Irish group (Table 5). Patients from all other ethnic groups combined admitted to ICU were significantly younger than patients from White Irish group (OR 50.85 vs 62.83, P = 0.012). Our hospital's catchment area serves a wide-ranging and diverse population with many ethnic minority groups represented. Our data demonstrated that there was a significant overrepresentation of a younger cohort of patients from ethnic minority groups admitted to ICU with COVID-19 infection with less co-morbidities than that of the White Irish group.
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Affiliation(s)
- Rhea O'Regan
- Department of Respiratory Medicine, Connolly Hospital Blanchardstown, RCSI Hospital Group, Dublin, Ireland.
| | - Finbarr Harnedy
- Department of Respiratory Medicine, Connolly Hospital Blanchardstown, RCSI Hospital Group, Dublin, Ireland
| | - Bearach Reynolds
- Department of Respiratory Medicine, Connolly Hospital Blanchardstown, RCSI Hospital Group, Dublin, Ireland
| | - Liam Cormican
- Department of Respiratory Medicine, Connolly Hospital Blanchardstown, RCSI Hospital Group, Dublin, Ireland
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Lei J, Yang J, Bao C, Lu F, Wu Q, Wu Z, Lv H, Zhou Y, Liu Y, Zhu N, Yu Y, Zhang Z, Hu M, Lin L. Isorhamnetin: what is the in vitro evidence for its antitumor potential and beyond? Front Pharmacol 2024; 15:1309178. [PMID: 38650631 PMCID: PMC11033395 DOI: 10.3389/fphar.2024.1309178] [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: 10/07/2023] [Accepted: 03/20/2024] [Indexed: 04/25/2024] Open
Abstract
Isorhamnetin (ISO) is a phenolic compound belonging to flavonoid family, showcasing important in vitro pharmacological activities such as antitumor, anti-inflammation, and organ protection. ISO is predominantly extracted from Hippophae rhamnoides L. This plant is well-known in China and abroad because of its "medicinal and food homologous" characteristics. As a noteworthy natural drug candidate, ISO has received considerable attention in recent years owing to its low cost, wide availability, high efficacy, low toxicity, and minimal side effects. To comprehensively elucidate the multiple biological functions of ISO, particularly its antitumor activities and other pharmacological potentials, a literature search was conducted using electronic databases including Web of Science, PubMed, Google Scholar, and Scopus. This review primarily focuses on ISO's ethnopharmacology. By synthesizing the advancements made in existing research, it is found that the general effects of ISO involve a series of in vitro potentials, such as antitumor, protection of cardiovascular and cerebrovascular, anti-inflammation, antioxidant, and more. This review illustrates ISO's antitumor and other pharmacological potentials, providing a theoretical basis for further research and new drug development of ISO.
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Affiliation(s)
- Jiaming Lei
- Key Laboratory of Environmental Related Diseases and One Health, School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning, China
| | - Jianbao Yang
- School of Public Health, Xianning Medical College, Hubei University of Science and Technology, Xianning, China
| | - Cuiyu Bao
- Hubei Province Key Laboratory on Cardiovascular, Cerebrovascular and Metabolic Disorder, Xianning Medical College, Hubei University of Science and Technology, Xianning, China
| | - Feifei Lu
- Key Laboratory of Environmental Related Diseases and One Health, School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning, China
| | - Qing Wu
- Key Laboratory of Environmental Related Diseases and One Health, School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning, China
| | - Zihan Wu
- School of Biomedical Engineering, Xianning Medical College, Hubei University of Science and Technology, Xianning, China
| | - Hong Lv
- School of Public Health, Xianning Medical College, Hubei University of Science and Technology, Xianning, China
| | - Yanhong Zhou
- Department of Medical School of Facial Features, Xianning Medical College, Hubei University of Science and Technology, Xianning, China
| | - Yifei Liu
- School of Biomedical Engineering, Xianning Medical College, Hubei University of Science and Technology, Xianning, China
| | - Ni Zhu
- Key Laboratory of Environmental Related Diseases and One Health, School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning, China
| | - You Yu
- Key Laboratory of Environmental Related Diseases and One Health, School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning, China
| | - Zhipeng Zhang
- Department of Medical School of Facial Features, Xianning Medical College, Hubei University of Science and Technology, Xianning, China
| | - Meichun Hu
- Key Laboratory of Environmental Related Diseases and One Health, School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning, China
| | - Li Lin
- Key Laboratory of Environmental Related Diseases and One Health, School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning, China
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Wang CH, Yang JS, Chen CJ, Su SH, Yu HY, Juan YN, Chiu YJ, Ho TJ. Protective effects of Jing-Si-herbal-tea in inflammatory cytokines-induced cell injury on normal human lung fibroblast via multiomic platform analysis. Tzu Chi Med J 2024; 36:152-165. [PMID: 38645788 PMCID: PMC11025590 DOI: 10.4103/tcmj.tcmj_267_23] [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: 10/24/2023] [Revised: 11/03/2023] [Accepted: 11/23/2023] [Indexed: 04/23/2024] Open
Abstract
OBJECTIVES The protective effects and related mechanisms of Jing-Si herbal tea (JSHT) were investigated in cellular damage mediated by pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, on normal human lung fibroblast by multiomic platform analysis. MATERIALS AND METHODS The in silico high-throughput target was analyzed using pharmacophore models by BIOVIA Discovery Studio 2022 with ingenuity pathway analysis software. To assess cell viability, the study utilized the MTT assay technique. In addition, the IncuCyte S3 ZOOM System was implemented for the continuous monitoring of cell confluence of JSHT-treated cytokine-injured HEL 299 cells. Cytokine concentrations were determined using a Quantibody Human Inflammation Array. Gene expression and signaling pathways were determined using next-generation sequencing. RESULTS In silico high-throughput target analysis of JSHT revealed ingenuity in canonical pathways and their networks. Glucocorticoid receptor signaling is a potential signaling of JSHT. The results revealed protective effects against the inflammatory cytokines on JSHT-treated HEL 299 cells. Transcriptome and network analyses revealed that induction of helper T lymphocytes, TNFSF12, NFKB1-mediated relaxin signaling, and G-protein coupled receptor signaling play important roles in immune regulatory on JSHT-treated cytokine-injured HEL 299 cells. CONCLUSION The findings from our research indicate that JSHT holds promise as a therapeutic agent, potentially offering advantageous outcomes in treating virus infections through various mechanisms. Furthermore, the primary bioactive components in JSHT justify extended research in antiviral drug development, especially in the context of addressing coronavirus.
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Affiliation(s)
- Chien-Hao Wang
- Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Jai-Sing Yang
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - Chao-Jung Chen
- Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
- Department of Medical Research, Proteomics Core Laboratory, China Medical University Hospital, Taichung, Taiwan
| | - San-Hua Su
- Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Hsin-Yuan Yu
- Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Yu-Ning Juan
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - Yu-Jen Chiu
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Tsung-Jung Ho
- Integration Center of Traditional Chinese and Modern Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan
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Zargari F, Mohammadi M, Nowroozi A, Morowvat MH, Nakhaei E, Rezagholi F. The Inhibitory Effects of the Herbals Secondary Metabolites (7α-acetoxyroyleanone, Curzerene, Incensole, Harmaline, and Cannabidiol) on COVID-19: A Molecular Docking Study. Recent Pat Biotechnol 2024; 18:316-331. [PMID: 38817009 DOI: 10.2174/0118722083246773231108045238] [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: 04/04/2023] [Revised: 09/29/2023] [Accepted: 10/03/2023] [Indexed: 06/01/2024]
Abstract
BACKGROUND Since the COVID-19 outbreak in early 2020, researchers and studies are continuing to find drugs and/or vaccines against the disease. As shown before, medicinal plants can be very good sources against viruses because of their secondary compounds which may cure diseases and help in survival of patients. There is a growing trend in the filed patents in this field. AIMS In the present study, we test and suggest the inhibitory potential of five herbal based extracts including 7α-acetoxyroyleanone, Curzerene, Incensole, Harmaline, and Cannabidiol with antivirus activity on the models of the significant antiviral targets for COVID-19 like spike glycoprotein, Papain-like protease (PLpro), non-structural protein 15 (NSP15), RNA-dependent RNA polymerase and core protease by molecular docking study. METHODS The Salvia rythida root was extracted, dried, and pulverized by a milling machine. The aqueous phase and the dichloromethane phase of the root extractive were separated by two-phase extraction using a separatory funnel. The separation was performed using the column chromatography method. The model of the important antivirus drug target of COVID-19 was obtained from the Protein Data Bank (PDB) and modified. TO study the binding difference between the studied molecules, the docking study was performed. RESULTS These herbal compounds are extracted from Salvia rhytidea, Curcuma zeodaria, Frankincense, Peganum harmala, and Cannabis herbs, respectively. The binding energies of all compounds on COVID-19 main targets are located in the limited area of 2.22-5.30 kcal/mol. This range of binding energies can support our hypothesis for the presence of the inhibitory effects of the secondary metabolites of mentioned structures on COVID-19. Generally, among the investigated herbal structures, Cannabidiol and 7α- acetoxyroyleanone compounds with the highest binding energy have the most inhibitory potential. The least inhibitory effects are related to the Curzerene and Incensole structures by the lowest binding affinity. CONCLUSION The general arrangement of the basis of the potential barrier of binding energies is in the order below: Cannabidiol > 7α-acetoxyroyleanone > Harmaline> Incensole > Curzerene. Finally, the range of docking scores for investigated herbal compounds on the mentioned targets indicates that the probably inhibitory effects on these targets obey the following order: main protease> RNA-dependent RNA polymerase> PLpro> NSP15> spike glycoprotein.
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Affiliation(s)
- Farshid Zargari
- Department of Chemistry, Faculty of Science, University of Sistan and Baluchestan (USB), P.O.Box 98135- 674, Zahedan, Iran
| | - Mehdi Mohammadi
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Box 71468-64685, Shiraz, Iran
| | - Alireza Nowroozi
- Department of Chemistry, Faculty of Science, University of Sistan and Baluchestan (USB), P.O.Box 98135- 674, Zahedan, Iran
| | - Mohammad Hossein Morowvat
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Box 71468-64685, Shiraz, Iran
| | - Ebrahim Nakhaei
- Department of Chemistry, Faculty of Science, University of Sistan and Baluchestan (USB), P.O.Box 98135- 674, Zahedan, Iran
| | - Fatemeh Rezagholi
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Box 71468-64685, Shiraz, Iran
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Wang Y, Shen M, Li Y, Shao J, Zhang F, Guo M, Zhang Z, Zheng S. COVID-19-associated liver injury: Adding fuel to the flame. Cell Biochem Funct 2023; 41:1076-1092. [PMID: 37947373 DOI: 10.1002/cbf.3883] [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: 08/23/2023] [Revised: 10/19/2023] [Accepted: 10/21/2023] [Indexed: 11/12/2023]
Abstract
COVID-19 is mainly characterized by respiratory disorders and progresses to multiple organ involvement in severe cases. With expansion of COVID-19 and SARS-CoV-2 research, correlative liver injury has been revealed. It is speculated that COVID-19 patients exhibited abnormal liver function, as previously observed in the SARS and MERS pandemics. Furthermore, patients with underlying diseases such as chronic liver disease are more susceptible to SARS-CoV-2 and indicate a poor prognosis accompanied by respiratory symptoms, systemic inflammation, or metabolic diseases. Therefore, COVID-19 has the potential to impair liver function, while individuals with preexisting liver disease suffer from much worse infected conditions. COVID-19 related liver injury may be owing to direct cytopathic effect, immune dysfunction, gut-liver axis interaction, and inappropriate medication use. However, discussions on these issues are infancy. Expanding research have revealed that angiotensin converting enzyme 2 (ACE2) expression mediated the combination of virus and target cells, iron metabolism participated in the virus life cycle and the fate of target cells, and amino acid metabolism regulated immune response in the host cells, which are all closely related to liver health. Further exploration holds great significance in elucidating the pathogenesis, facilitating drug development, and advancing clinical treatment of COVID-19-related liver injury. This article provides a review of the clinical and laboratory hepatic characteristics in COVID-19 patients, describes the etiology and impact of liver injury, and discusses potential pathophysiological mechanisms.
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Affiliation(s)
- Yingqian Wang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Min Shen
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China
| | - Yujia Li
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Jiangjuan Shao
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Feng Zhang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Mei Guo
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Zili Zhang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Shizhong Zheng
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
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Zhang S, Liu X, Zhao Y, Wang P, Yu R, Xu P, Jiang Y, Cheng L. Microbiome characteristics description of COVID-19 patients based on bulk RNA-seq and scRNA-Seq data. Comput Biol Med 2023; 165:107400. [PMID: 37651767 DOI: 10.1016/j.compbiomed.2023.107400] [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: 07/16/2023] [Revised: 08/04/2023] [Accepted: 08/26/2023] [Indexed: 09/02/2023]
Abstract
After infection with SARS-CoV-2, the microbiome inside the human body changes dramatically. By re-annotating microbial sequences in bulk RNA-seq and scRNA-seq data of COVID-19 patients, we described the cellular microbial landscape of COVID-19 patients and identified characteristic microorganisms in various tissues. We found that Acinetobacter lwoffii was highly correlated with COVID-19 symptoms and might disrupt some pathways of patients by interacting with the host and other microbes, such as Klebsiella pneumoniae. We further identified characteristic microorganisms specific to cell type, indicating the enrichment preference of some microbes. We also revealed the co-infection of SARS-CoV-2 with hMPV, which may cause the development of COVID-19. Overall, we demonstrated that the presence of intracellular microorganisms in COVID-19 patients and the synergies between microorganisms were strongly correlated with disease progression, providing a theoretical basis for COVID-19 treatment in a certain extent.
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Affiliation(s)
- Sainan Zhang
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, Heilongjiang, China.
| | - Xingwang Liu
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, Heilongjiang, China.
| | - Yue Zhao
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, Heilongjiang, China.
| | - Ping Wang
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, Heilongjiang, China.
| | - Rui Yu
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, Heilongjiang, China.
| | - Peigang Xu
- Chongqing Research Institute of Harbin Institute of Technology, China.
| | - Yue Jiang
- Cipher Gene, Ltd., Beijing, 100080, China.
| | - Liang Cheng
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, Heilongjiang, China; NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, 150028, Heilongjiang, China.
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11
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Zwicklbauer K, Krentz D, Bergmann M, Felten S, Dorsch R, Fischer A, Hofmann-Lehmann R, Meli ML, Spiri AM, Alberer M, Kolberg L, Matiasek K, Zablotski Y, von Both U, Hartmann K. Long-term follow-up of cats in complete remission after treatment of feline infectious peritonitis with oral GS-441524. J Feline Med Surg 2023; 25:1098612X231183250. [PMID: 37548535 PMCID: PMC10811998 DOI: 10.1177/1098612x231183250] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/08/2023]
Abstract
OBJECTIVES Feline infectious peritonitis (FIP), a common disease in cats caused by feline coronavirus (FCoV), is usually fatal once clinical signs appear. Successful treatment of FIP with oral GS-441524 for 84 days was demonstrated recently by this research group. The aim of this study was to evaluate the long-term outcome in these cats. METHODS A total of 18 successfully treated cats were followed for up to 1 year after treatment initiation (9 months after completion of the antiviral treatment). Follow-up examinations were performed at 12-week intervals, including physical examination, haematology, serum biochemistry, abdominal and thoracic ultrasound, FCoV ribonucleic acid (RNA) loads in blood and faeces by reverse transciptase-quantitative PCR and anti-FCoV antibody titres by indirect immunofluorescence assay. RESULTS Follow-up data were available from 18 cats in week 24, from 15 cats in week 36 and from 14 cats in week 48 (after the start of treatment), respectively. Laboratory parameters remained stable after the end of the treatment, with undetectable blood viral loads (in all but one cat on one occasion). Recurrence of faecal FCoV shedding was detected in five cats. In four cats, an intermediate short-term rise in anti-FCoV antibody titres was detected. In total, 12 cats showed abdominal lymphadenomegaly during the follow-up period; four of them continuously during the treatment and follow-up period. Two cats developed mild neurological signs, compatible with feline hyperaesthesia syndrome, in weeks 36 and 48, respectively; however, FCoV RNA remained undetectable in blood and faeces, and no increase in anti-FCoV antibody titres was observed in these two cats, and the signs resolved. CONCLUSIONS AND RELEVANCE Treatment with GS-441524 proved to be effective against FIP in both the short term as well as the long term, with no confirmed relapse during the 1-year follow-up period. Whether delayed neurological signs could be a long-term adverse effect of the treatment or associated with a 'long FIP syndrome' needs to be further evaluated.
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Affiliation(s)
- Katharina Zwicklbauer
- Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, Munich, Germany
| | - Daniela Krentz
- Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, Munich, Germany
| | - Michèle Bergmann
- Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, Munich, Germany
| | - Sandra Felten
- Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, Munich, Germany
| | - Roswitha Dorsch
- Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, Munich, Germany
| | - Andrea Fischer
- Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, Munich, Germany
| | - Regina Hofmann-Lehmann
- Clinical Laboratory, Department of Clinical Diagnostics and Services, Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
| | - Marina L Meli
- Clinical Laboratory, Department of Clinical Diagnostics and Services, Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
| | - Andrea M Spiri
- Clinical Laboratory, Department of Clinical Diagnostics and Services, Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
| | - Martin Alberer
- Division of Paediatric Infectious Diseases, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany
| | - Laura Kolberg
- Division of Paediatric Infectious Diseases, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany
| | - Kaspar Matiasek
- Section of Clinical and Comparative Neuropathology, Institute of Veterinary Pathology, Centre for Clinical Veterinary Medicine, LMU Munich, Munich, Germany
| | - Yury Zablotski
- Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, Munich, Germany
| | - Ulrich von Both
- Division of Paediatric Infectious Diseases, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany
- German Center for Infection Research (DZIF), partner site Munich, Munich, Germany
| | - Katrin Hartmann
- Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, Munich, Germany
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12
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Sinha PR, Mallick N, Sahu RL. Avascular Necrosis of the Hip after the COVID-19 Pandemic. JOURNAL OF PHARMACY AND BIOALLIED SCIENCES 2023; 15:S661-S664. [PMID: 37654323 PMCID: PMC10466589 DOI: 10.4103/jpbs.jpbs_87_23] [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: 01/30/2023] [Revised: 02/02/2023] [Accepted: 02/08/2023] [Indexed: 09/02/2023] Open
Abstract
Background and Objectives It is clear that COVID-19 can have a wide range of effects on the body, and the musculoskeletal system is no exception. Studies are ongoing to better understand how the virus may impact the hip bone and joint tissue. However, it is known that COVID-19 can cause inflammation and damage to various parts of the body, including the bones and joints, which could lead to pain, stiffness, and other symptoms. Materials and Methods A retrospective analysis is done with ten patients admitted to the hospital due to COVID-19 and later complained of hip pain. Magnetic resonance imaging (MRI) was performed on the patients, and it was found that they had degenerative changes characterized by avascular necrosis (AVN) of the head of the femur. One of the patients had a history of previous surgery on the femur with a plate and screws and was doing well but developed AVN after contracting COVID-19. Results Observation among these groups shows a strong association between the history of COVID-19, high levels of IgG antibodies, the presence of joint abnormalities, and moderately severe symptoms. There is no evidence of identifying autoimmune, degenerative, or AVN diseases. This set of patients responded positively to supportive therapy and anti-inflammatory drugs used in empirical treatment, which subsided joint pain and acute inflammatory symptoms. Conclusions It has been determined that there are significant musculoskeletal complications in COVID-19 patients, including AVN, which may be caused by the high use of steroids and microembolism leading to bone necrosis. Therefore, further studies and long-term follow-up are recommended.
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Affiliation(s)
- Priti R. Sinha
- Department of Orthopaedics, GS Medical College and Hospital, Pilkhuwa, Hapur, Uttar Pradesh, India
| | - Nitin Mallick
- Department of Orthopaedics, Santosh Medical College, Ghaziabad, Uttar Pradesh, India
| | - Ramjee L. Sahu
- Department of Orthopaedics, Saraswati Institute of Medical Sciences, Pilkhuwa, Hapur, Uttar Pradesh, India
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13
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Shehzadi K, Saba A, Yu M, Liang J. Structure-Based Drug Design of RdRp Inhibitors against SARS-CoV-2. Top Curr Chem (Cham) 2023; 381:22. [PMID: 37318607 DOI: 10.1007/s41061-023-00432-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 05/15/2023] [Indexed: 06/16/2023]
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic since 2019, spreading rapidly and posing a significant threat to human health and life. With over 6 billion confirmed cases of the virus, the need for effective therapeutic drugs has become more urgent than ever before. RNA-dependent RNA polymerase (RdRp) is crucial in viral replication and transcription, catalysing viral RNA synthesis and serving as a promising therapeutic target for developing antiviral drugs. In this article, we explore the inhibition of RdRp as a potential treatment for viral diseases, analysing the structural information of RdRp in virus proliferation and summarizing the reported inhibitors' pharmacophore features and structure-activity relationship profiles. We hope that the information provided by this review will aid in structure-based drug design and aid in the global fight against SARS-CoV-2 infection.
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Affiliation(s)
- Kiran Shehzadi
- Key Laboratory of Medical Molecule Science and Pharmaceutical Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 10081, China
| | - Afsheen Saba
- Key Laboratory of Medical Molecule Science and Pharmaceutical Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 10081, China
| | - Mingjia Yu
- Key Laboratory of Medical Molecule Science and Pharmaceutical Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 10081, China.
| | - Jianhua Liang
- Key Laboratory of Medical Molecule Science and Pharmaceutical Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 10081, China.
- Yangtze Delta Region Academy of Beijing Institute of Technology, Jiaxing, 314019, China.
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14
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Choudhary P, Singh T, Amod A, Singh S. Evaluation of phytoconstituents of Tinospora cordifolia against K417N and N501Y mutant spike glycoprotein and main protease of SARS-CoV-2- an in silico study. J Biomol Struct Dyn 2023; 41:4106-4123. [PMID: 35467486 DOI: 10.1080/07391102.2022.2062787] [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: 12/02/2021] [Accepted: 04/02/2022] [Indexed: 10/18/2022]
Abstract
Coronavirus disease 2019 (COVID-19) caused appalling conditions over the globe, which is currently faced by the entire human population. One of the primary reasons behind the uncontrollable situation is the lack of specific therapeutics. In such conditions, drug repurposing of available drugs (viz. Chloroquine, Lopinavir, etc.) has been proposed, but various clinical and preclinical investigations indicated the toxicity and adverse side effects of these drugs. This study explores the inhibition potency of phytochemicals from Tinospora cordifolia (Giloy) against SARS CoV-2 drugable targets (spike glycoprotein and Mpro proteins) using molecular docking and MD simulation studies. ADMET, virtual screening, MD simulation, postsimulation analysis (RMSD, RMSF, Rg, SASA, PCA, FES) and MM-PBSA calculations were carried out to predict the inhibition efficacy of the phytochemicals against SARS CoV-2 targets. Tinospora compounds showed better binding affinity than the corresponding reference. Their binding affinity ranges from -9.63 to -5.68 kcal/mole with spike protein and -10.27 to -7.25 kcal/mole with main protease. Further 100 ns exhaustive simulation studies and MM-PBSA calculations supported favorable and stable binding of them. This work identifies Nine Tinospora compounds as potential inhibitors. Among those, 7-desacetoxy-6,7-dehydrogedunin was found to inhibit both spike (7NEG) and Mpro (7MGS and 6LU7) proteins, and Columbin was found to inhibit selected spike targets (7NEG and 7NX7). In all the analyses, these compounds performed well and confirms the stable binding. Hence the identified compounds, advocated as potential inhibitors can be taken for further in vitro and in vivo experimental validation to determine their anti-SARS-CoV-2 potential.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Princy Choudhary
- Applied Science Department, Indian Institute of Information Technology, Allahabad, Uttar Pradesh, India
| | - Tanu Singh
- Applied Science Department, Indian Institute of Information Technology, Allahabad, Uttar Pradesh, India
| | - Ayush Amod
- Applied Science Department, Indian Institute of Information Technology, Allahabad, Uttar Pradesh, India
| | - Sangeeta Singh
- Applied Science Department, Indian Institute of Information Technology, Allahabad, Uttar Pradesh, India
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15
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Velagacherla V, Suresh A, Mehta CH, Nayak UY, Nayak Y. Multi-Targeting Approach in Selection of Potential Molecule for COVID-19 Treatment. Viruses 2023; 15:213. [PMID: 36680253 PMCID: PMC9861341 DOI: 10.3390/v15010213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 01/05/2023] [Accepted: 01/06/2023] [Indexed: 01/15/2023] Open
Abstract
The coronavirus disease (COVID-19) is a pandemic that started in the City of Wuhan, Hubei Province, China, caused by the spread of coronavirus (SARS-CoV-2). Drug discovery teams around the globe are in a race to develop a medicine for its management. It takes time for a novel molecule to enter the market, and the ideal way is to exploit the already approved drugs and repurpose them therapeutically. We have attempted to screen selected molecules with an affinity towards multiple protein targets in COVID-19 using the Schrödinger suit for in silico predictions. The proteins selected were angiotensin-converting enzyme-2 (ACE2), main protease (MPro), and spike protein. The molecular docking, prime MM-GBSA, induced-fit docking (IFD), and molecular dynamics (MD) simulations were used to identify the most suitable molecule that forms a stable interaction with the selected viral proteins. The ligand-binding stability for the proteins PDB-IDs 1ZV8 (spike protein), 5R82 (Mpro), and 6M1D (ACE2), was in the order of nintedanib > quercetin, nintedanib > darunavir, nintedanib > baricitinib, respectively. The MM-GBSA, IFD, and MD simulation studies imply that the drug nintedanib has the highest binding stability among the shortlisted. Nintedanib, primarily used for idiopathic pulmonary fibrosis, can be considered for repurposing for us against COVID-19.
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Affiliation(s)
- Varalakshmi Velagacherla
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Udupi 576104, India
| | - Akhil Suresh
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Udupi 576104, India
| | - Chetan Hasmukh Mehta
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Udupi 576104, India
| | - Usha Y. Nayak
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Udupi 576104, India
- Manipal Centre for Infectious Diseases, Prasanna School of Public Health, Manipal Academy of Higher Education, Udupi 576104, India
| | - Yogendra Nayak
- Manipal Centre for Infectious Diseases, Prasanna School of Public Health, Manipal Academy of Higher Education, Udupi 576104, India
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Udupi 576104, India
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16
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Manóchio C, Torres-Loureiro S, Scudeler MM, Miwa B, Souza-Santos FC, Rodrigues-Soares F. Theranostics for COVID-19 Antiviral Drugs: Prospects and Challenges for Worldwide Precision/Personalized Medicine. OMICS : A JOURNAL OF INTEGRATIVE BIOLOGY 2023; 27:6-14. [PMID: 36602768 DOI: 10.1089/omi.2022.0151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Coronavirus disease 2019 (COVID-19) is a systemic disease that impacts multiple organ systems with a complex clinical presentation and outcomes that can vary from person to person and between populations. To optimize COVID-19 treatment outcomes, and in light of the availability of antiviral drugs, there is a need for greater attention to the field of theranostics, the fusion of therapeutics and diagnostics. Theranostics tests would be invaluable, we suggest in this expert review, so as to optimize the efficacy and safety of current and future antiviral drugs against COVID-19. Theranostics would also assist in the design and implementation of clinical trials with antiviral drug candidates. We discuss here theranostics considering drugs such as remdesivir, Paxlovid™, and molnupiravir. All in all, we underscore that theranostics as a concept and practice is essential for efficient and safe health interventions against COVID-19 and other ecological crises in the 21st century.
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Affiliation(s)
- Caíque Manóchio
- Departamento de Patologia, Genética e Evolução, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Uberaba, Brazil
| | - Sabrina Torres-Loureiro
- Departamento de Patologia, Genética e Evolução, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Uberaba, Brazil
| | - Mariana M Scudeler
- Departamento de Patologia, Genética e Evolução, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Uberaba, Brazil
| | - Bruno Miwa
- Departamento de Patologia, Genética e Evolução, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Uberaba, Brazil.,Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Fernanda C Souza-Santos
- Departamento de Patologia, Genética e Evolução, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Uberaba, Brazil
| | - Fernanda Rodrigues-Soares
- Departamento de Patologia, Genética e Evolução, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Uberaba, Brazil
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17
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Babazadeh Z. Involvement of NLRP3 Inflammasome in SARS-Cov-2-Induced Multiorgan Dysfunction in Patients with COVID-19: A Review of Molecular Mechanisms. TANAFFOS 2023; 22:40-52. [PMID: 37920322 PMCID: PMC10618576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Accepted: 07/13/2022] [Indexed: 11/04/2023]
Abstract
Nucleotide-binding domain and leucine-rich repeat protein- 3 (NLRP3) inflammasome is a critical component of the innate immune system. The inflammasome activation is correlated with the COVID- 19 severity. Furthermore, the underlying conditions are accompanied by hyperactivation of NLRP3 inflammasome and poor outcomes. Herein, we presented the involvement of NLRP3 inflammasome in the pathogenies of SARS-CoV-2-induced multiorgan dysfunction and potential therapeutics. Overexpression of NLRP3 inflammasome components and subsequently increased levels of cytokines following viral infection leads to the cytokine storm and indirectly affects the organ functions. Besides, invading host cells via SARS-CoV-2 further activates the NLRP3 inflammasome and induces pyroptosis in immune cells, resulting in the secretion of higher levels of proinflammatory cytokines into the extracellular matrix. These events continued by induction of fibrosis and organ dysfunction following infection with SARS-CoV-2 in critically ill patients. This condition can be observed in individuals with comorbidities (e.g., diabetes, obesity, etc.) due to a primed state of immunity, which can cause severe disease or death in this population. Therefore, understanding the mechanisms underlying host-SARS-CoV-2 interaction may help to clarify the pathophysiology of SARS-CoV-2- induced multiorgan dysfunction and introduce potential therapeutic strategies.
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Affiliation(s)
- Zahra Babazadeh
- Department of Anatomical Science, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
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18
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Chen L, Lin D, Xu H, Li J, Lin L. WLLP: A weighted reconstruction-based linear label propagation algorithm for predicting potential therapeutic agents for COVID-19. Front Microbiol 2022; 13:1040252. [PMID: 36466666 PMCID: PMC9713947 DOI: 10.3389/fmicb.2022.1040252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Accepted: 10/06/2022] [Indexed: 11/18/2022] Open
Abstract
The global coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV) has led to a huge health and economic crises. However, the research required to develop new drugs and vaccines is very expensive in terms of labor, money, and time. Owing to recent advances in data science, drug-repositioning technologies have become one of the most promising strategies available for developing effective treatment options. Using the previously reported human drug virus database (HDVD), we proposed a model to predict possible drug regimens based on a weighted reconstruction-based linear label propagation algorithm (WLLP). For the drug–virus association matrix, we used the weighted K-nearest known neighbors method for preprocessing and label propagation of the network based on the linear neighborhood similarity of drugs and viruses to obtain the final prediction results. In the framework of 10 times 10-fold cross-validated area under the receiver operating characteristic (ROC) curve (AUC), WLLP exhibited excellent performance with an AUC of 0.8828 ± 0.0037 and an area under the precision-recall curve of 0.5277 ± 0.0053, outperforming the other four models used for comparison. We also predicted effective drug regimens against SARS-CoV-2, and this case study showed that WLLP can be used to suggest potential drugs for the treatment of COVID-19.
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Affiliation(s)
- Langcheng Chen
- Center of Campus Network and Modern Educational Technology, Guangdong University of Technology, Guangzhou, China
| | - Dongying Lin
- School of Computer Science, Guangdong University of Technology, Guangzhou, China
| | - Haojie Xu
- School of Computer Science, Guangdong University of Technology, Guangzhou, China
| | - Jianming Li
- School of Computer Science, Guangdong University of Technology, Guangzhou, China
| | - Lieqing Lin
- Center of Campus Network and Modern Educational Technology, Guangdong University of Technology, Guangzhou, China
- *Correspondence: Lieqing Lin
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19
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Yi Y, Fang J, Liu Y, Gao Y, Lin W, Hao D, Zhang X, Zhang M. Clinical Characteristics of 254 COVID-19 Inpatients in Yichang, Hubei, China, and Efficacy of Integrated Chinese and Western Medicine Treatment. Int J Gen Med 2022; 15:8191-8200. [PMID: 36411815 PMCID: PMC9675424 DOI: 10.2147/ijgm.s391024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Accepted: 11/02/2022] [Indexed: 11/16/2022] Open
Abstract
Introduction There is no effective treatment plan for coronavirus disease 2019 (COVID-19). We employed a combination of Chinese and Western medicine treatment for some COVID-19 inpatients. Methods This study was a prospective cohort study that observed non-critical COVID-19 inpatients. The differences will be observed in the time from admission to two consecutive 2019-nCoV nucleic acid test negatives and the Visual Analog Scale (VAS) score between the two groups. Results A total of 254 confirmed COVID-19 patients were included in this study. The median time from the admission to two consecutive negative nucleic acid tests was 14 days for the integrated Chinese and Western Medicine (ICWM) group, while the Western Medicine (WM) group was 16 days. Besides, the median VAS score of the ICWM group was 0, which was an average decrease of 2 points compared to the time of admission. Conclusion For non-critical COVID-19 patients, it was safe and have more benefits to add traditional Chinese medicine decoction based on WM treatment.
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Affiliation(s)
- Yongxin Yi
- Department of Encephalopathy, the Third People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China
| | - Jiayang Fang
- Department of Encephalopathy, the Third People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China
| | - Yunzhu Liu
- Department of Encephalopathy, the Third People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China
| | - Yidong Gao
- Department of Encephalopathy, the Third People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China
| | - Weizhi Lin
- Department of Encephalopathy, the Third People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China
| | - Dongdong Hao
- Department of Outpatient, Lanzhou 7th Rest Center for Retired Cadre, Gansu Military Region, Lanzhou, People’s Republic of China
| | - Xing Zhang
- Department of Medicine, the State Key Laboratory of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd, Nanjing, People’s Republic of China
- Department of Medicine, Nanjing Simcere Medical Laboratory Science Co., Ltd, Nanjing, People’s Republic of China
| | - Min Zhang
- Department of Encephalopathy, the Third People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China
- Correspondence: Min Zhang, Department of Encephalopathy, the Third People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China, Email
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20
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Abadi B, Aarabi Jeshvaghani AH, Fathalipour H, Dehghan L, Rahimi Sirjani K, Forootanfar H. Therapeutic Strategies in the Fight against COVID-19: From Bench to Bedside. IRANIAN JOURNAL OF MEDICAL SCIENCES 2022; 47:517-532. [PMID: 36380976 PMCID: PMC9652495 DOI: 10.30476/ijms.2021.92662.2396] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Revised: 11/17/2021] [Accepted: 12/10/2021] [Indexed: 06/16/2023]
Abstract
In December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China. This virus rapidly spread worldwide and was declared a global pandemic by the World Health Organization (WHO) in March 2020. High incidence, long incubation period, and diverse clinical signs of the disease posed a huge challenge globally. The efforts of health systems have been focused on repurposing existing drugs or developing innovative therapies to reduce the morbidity and mortality associated with SARS-CoV-2. In addition, most of the large pharmaceutical companies are intensely working on vaccine development to swiftly deliver safe and effective vaccines to prevent further spread of the virus. In this review, we will discuss the latest data on therapeutic strategies undergoing clinical trials. Additionally, we will provide a summary of vaccines currently under development.
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Affiliation(s)
- Banafshe Abadi
- Pharmaceutical Sciences and Cosmetic Products Research Center, Kerman University of Medical Sciences, Kerman, Iran
- Brain Cancer Research Core, Universal Scientific Education and Research Network, Tehran, Iran
| | | | - Hadis Fathalipour
- Pharmaceutical Sciences and Cosmetic Products Research Center, Kerman University of Medical Sciences, Kerman, Iran
- Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran
| | - Leili Dehghan
- Department of Pharmaceutical Biotechnology, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
| | | | - Hamid Forootanfar
- Pharmaceutical Sciences and Cosmetic Products Research Center, Kerman University of Medical Sciences, Kerman, Iran
- Department of Pharmaceutical Biotechnology, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
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21
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Guo Y, Ma A, Wang X, Yang C, Chen X, Li G, Qiu F. Research progress on the antiviral activities of natural products and their derivatives: Structure–activity relationships. Front Chem 2022; 10:1005360. [PMID: 36311429 PMCID: PMC9596788 DOI: 10.3389/fchem.2022.1005360] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Accepted: 09/28/2022] [Indexed: 11/23/2022] Open
Abstract
Viruses spread rapidly and are well-adapted to changing environmental events. They can infect the human body readily and trigger fatal diseases. A limited number of drugs are available for specific viral diseases, which can lead to non-efficacy against viral variants and drug resistance, so drugs with broad-spectrum antiviral activity are lacking. In recent years, a steady stream of new viral diseases has emerged, which has prompted development of new antiviral drugs. Natural products could be employed to develop new antiviral drugs because of their innovative structures and broad antiviral activities. This review summarizes the progress of natural products in antiviral research and their bright performance in drug resistance issues over the past 2 decades. Moreover, it fully discusses the effect of different structural types of natural products on antiviral activity in terms of structure–activity relationships. This review could provide a foundation for the development of antiviral drugs.
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Affiliation(s)
- Yajing Guo
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Anna Ma
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xinyan Wang
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Chen Yang
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xi Chen
- School of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- *Correspondence: Xi Chen, ; Gen Li,
| | - Gen Li
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- *Correspondence: Xi Chen, ; Gen Li,
| | - Feng Qiu
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjfin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
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22
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Bhat SA, Shibata T, Leong M, Plummer J, Vail E, Khan Z. Comparative Upper Respiratory Tract Transcriptomic Profiling Reveals a Potential Role of Early Activation of Interferon Pathway in Severe COVID-19. Viruses 2022; 14:v14102182. [PMID: 36298737 PMCID: PMC9608318 DOI: 10.3390/v14102182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 09/24/2022] [Accepted: 09/28/2022] [Indexed: 11/07/2022] Open
Abstract
Infection with SARS-CoV-2 results in Coronavirus disease 2019 (COVID-19) is known to cause mild to acute respiratory infection and sometimes progress towards respiratory failure and death. The mechanisms driving the progression of the disease and accumulation of high viral load in the lungs without initial symptoms remain elusive. In this study, we evaluated the upper respiratory tract host transcriptional response in COVID-19 patients with mild to severe symptoms and compared it with the control COVID-19 negative group using RNA-sequencing (RNA-Seq). Our results reveal an upregulated early type I interferon response in severe COVID-19 patients as compared to mild or negative COVID-19 patients. Moreover, severely symptomatic patients have pronounced induction of interferon stimulated genes (ISGs), particularly the oligoadenylate synthetase (OAS) family of genes. Our results are in concurrence with other studies depicting the early induction of IFN-I response in severe COVID-19 patients, providing novel insights about the ISGs involved.
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Affiliation(s)
- Shabir A. Bhat
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Tomohiro Shibata
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Matthew Leong
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Jasmine Plummer
- The Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Eric Vail
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Zakir Khan
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Correspondence: ; Tel.: +1-(310)-423-7768
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The Prevalence of Electrolyte Imbalances and Their Relationship with Disease Severity in Hospitalized COVID-19 Patients. ARCHIVES OF CLINICAL INFECTIOUS DISEASES 2022. [DOI: 10.5812/archcid-112190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
: Since the identification of COVID-19, its various manifestations have been reported in numerous studies. However, few studies have specifically examined the electrolyte imbalances seen in this disease. Patients with a definitive diagnosis of COVID-19 admitted to our hospital entered this retrospective cross-sectional study. Upon admission of the patients, a blood sample was sent for the analysis of the electrolytes. The relationship between electrolyte imbalances and disease severity, ICU admission, and mortality was also stated. Of 1072 hospitalized patients studied, 657 were men, and 415 were women. The prevalence of hypocalcemia (47.7%), hypophosphatemia (21.1%), hypomagnesemia (15.8%), and hyponatremia (13%) was higher compared to other electrolyte imbalances in these patients. Lower levels of sodium, calcium, and magnesium were seen in severe cases, while higher serum levels of potassium and phosphorus were detected in severe cases and ICU hospitalized patients. Causes such as albumin decrease in inflammation, the role of PTH, and the effect of vitamin D can play a role in hypocalcemia in these patients. In addition, electrolyte loss from the digestive tract can contribute to electrolyte imbalances. Because of the high prevalence of electrolyte imbalance in these patients, electrolyte monitoring is recommended in COVID-19 patients to ensure better care.
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Kapil K, Muntode Gharde P. A Review on Effectiveness of Plasma Therapy in Severe COVID-19 Patients. Cureus 2022; 14:e28914. [PMID: 36237760 PMCID: PMC9547123 DOI: 10.7759/cureus.28914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Accepted: 09/07/2022] [Indexed: 12/04/2022] Open
Abstract
Coronavirus 2019 has created a big threat to the modern world. Many researchers and scientists had taken the burden of finding information about this entity, its structure, its transmission, and also about the treatment that can be given to individuals infected by it. There has been use of different medicines at different times simultaneously researching about them, starting with only symptomatic and supportive treatment, then antimalarial agents like chloroquine and hydroxychloroquine, then going to favipavir, and other antivirals, then came the use of vaccines and also convalescent plasma therapy for COVID-19. The most advanced is convalescent plasma use for the treating coronavirus. Using plasma of patients who have remitted from this disease and putting it into those individuals who are dealing with the disease or are critically ill for improvement of their health status. This treatment has been used for many other diseases too and has been proven efficacious. So, this technique is being used and studied for coronavirus 2019 as well. There have been set certain criteria for those who can donate plasma and also criteria for the recipients of this technique. Also, there can be adverse reactions or even side effects with this, like transfusion-related acute lung injury (TRALI), so they should also be kept in mind during treatment with this method. So, though there are many methods to date to treat these individuals but one of the latest ones is using plasma, which is proven to be efficacious but still many studies are under process for the same.
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Efficacy and safety of nitazoxanide in treating SARS-CoV-2 infection: a systematic review and meta-analysis of blinded, placebo-controlled, randomized clinical trials. Eur J Clin Pharmacol 2022; 78:1813-1821. [PMID: 36066651 PMCID: PMC9446612 DOI: 10.1007/s00228-022-03380-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Accepted: 08/30/2022] [Indexed: 12/15/2022]
Abstract
Purpose Nitazoxanide is a broad-spectrum antiparasitic that has been tested for COVID-19 due to its anti-inflammatory effects and in vitro antiviral activity. This study synthesized the best evidence on the efficacy and safety of nitazoxanide in COVID-19. Methods Searches for studies were performed in peer-reviewed and grey-literature from January 1, 2020 to May 23, 2022. The following elements were used to define eligibility criteria: (1) Population: individuals with COVID-19; (2) Intervention: nitazoxanide; (3) Comparison: placebo; (4) Outcomes: primary outcome was death, and secondary outcomes were viral load, positive RT-PCR status, serum biomarkers of inflammation, composite measure of disease progression (ICU admission or invasive mechanical ventilation), and any adverse events; (5) Study type: blinded, placebo-controlled, randomized clinical trials (RCTs). Treatment effects were reported as relative risk (RR) for dichotomous variables and standardized mean difference (SMD) for continuous variables with 95% confidence intervals (CI). Results Five blinded, placebo-controlled RCTs were included and enrolled individuals with mild or moderate SARS-CoV-2 infection. We found no difference between nitazoxanide and placebo in reducing viral load (SMD = − 0.16; 95% CI − 0.38 to 0.05) and the frequency of positive RTP-PCR results (RR = 0.92; 95% CI 0.81 to 1.06). In addition, there was no decreased risk for disease progression (RR = 0.63; 95% CI 0.38 to 1.04) and death (RR = 0.81; 95% CI 0.36 to 1.78) among patients receiving nitazoxanide. Patients with COVID-19 treated with nitazoxanide had decreased levels of white blood cells (SMD = − 0.15; 95% − 0.29 to − 0.02), lactate dehydrogenase (LDH) (SMD − 0.32; 95% − 0.52 to − 0.13), and D-dimer (SMD − 0.49; 95% CI − 0.68 to − 0.31) compared to placebo, but the magnitude of effect was considered small to moderate. Conclusion This systematic review showed no evidence of clinical benefits of the use of nitazoxanide to treat patients with mild or moderate COVID-19. In addition, we found a reduction in WBC, LDH, and D-dimer levels among nitazoxanide-treated patients, but the effect size was considered small to moderate. Supplementary Information The online version contains supplementary material available at 10.1007/s00228-022-03380-5.
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Topchiy TВ, Ardatskaya MD, Butorova LI, Маslovskii LV, Мinushkin ОN. Features of the intestine conditions at patients with a new coronavirus infection. TERAPEVT ARKH 2022; 94:920-926. [DOI: 10.26442/00403660.2022.07.201768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 08/12/2022] [Indexed: 11/22/2022]
Abstract
COVID-19 infection may present with gastrointestinal lesions in up to 25% of patients. One of the target organs of the SARS-CoV-2 virus is the intestine. The pathogenesis of intestinal damage in a new coronavirus infection remains unclear and requires further in-depth study. Possible mechanisms include a direct cytotoxic effect of the virus, a persistent reduction in butyrate-producing bacteria, side effects of drugs, Clostridioides difficile infection, microvascular thrombosis, and the immune-mediated inflammatory reactions in the intestine. The most common symptom of intestinal damage during coronavirus infection, both in the acute phase and in the post-COVID period, is diarrhea. The impact of many aggressive factors on the intestines can form both long-term functional disorders and be the cause of the onset of organic diseases. Treatment should be aimed at possible causes of intestinal damage (Clostridioides difficile), as well as reducing inflammation, restoring intestinal permeability, cytoprotection of mucosal cells, replenishing butyric acid deficiency. When choosing a therapy for intestinal disorders, preference should be given to drugs with a pleiotropic effect in order to influence various possible pathogenetic mechanisms.
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Krisanova N, Pozdnyakova N, Pastukhov A, Dudarenko M, Shatursky O, Gnatyuk O, Afonina U, Pyrshev K, Dovbeshko G, Yesylevskyy S, Borisova T. Amphiphilic anti-SARS-CoV-2 drug remdesivir incorporates into the lipid bilayer and nerve terminal membranes influencing excitatory and inhibitory neurotransmission. BIOCHIMICA ET BIOPHYSICA ACTA. BIOMEMBRANES 2022; 1864:183945. [PMID: 35461828 PMCID: PMC9023372 DOI: 10.1016/j.bbamem.2022.183945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 04/03/2022] [Accepted: 04/17/2022] [Indexed: 12/05/2022]
Abstract
Remdesivir is a novel antiviral drug, which is active against the SARS-CoV-2 virus. Remdesivir is known to accumulate in the brain but it is not clear whether it influences the neurotransmission. Here we report diverse and pronounced effects of remdesivir on transportation and release of excitatory and inhibitory neurotransmitters in rat cortex nerve terminals (synaptosomes) in vitro. Direct incorporation of remdesivir molecules into the cellular membranes was shown by FTIR spectroscopy, planar phospholipid bilayer membranes and computational techniques. Remdesivir decreases depolarization-induced exocytotic release of L-[14C] glutamate and [3H] GABA, and also [3H] GABA uptake and extracellular level in synaptosomes in a dose-dependent manner. Fluorimetric studies confirmed remdesivir-induced impairment of exocytosis in nerve terminals and revealed a decrease in synaptic vesicle acidification. Our data suggest that remdesivir dosing during antiviral therapy should be precisely controlled to prevent possible neuromodulatory action at the presynaptic level. Further studies of neurotropic and membranotropic effects of remdesivir are necessary.
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Affiliation(s)
- Natalia Krisanova
- The Department of Neurochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, 9 Leontovicha Str., Kyiv 01054, Ukraine
| | - Natalia Pozdnyakova
- The Department of Neurochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, 9 Leontovicha Str., Kyiv 01054, Ukraine
| | - Artem Pastukhov
- The Department of Neurochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, 9 Leontovicha Str., Kyiv 01054, Ukraine
| | - Marina Dudarenko
- The Department of Neurochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, 9 Leontovicha Str., Kyiv 01054, Ukraine
| | - Oleg Shatursky
- The Department of Neurochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, 9 Leontovicha Str., Kyiv 01054, Ukraine
| | - Olena Gnatyuk
- The Department of Physics of biological systems, Institute of Physics, NAS of Ukraine, 46 Nauky Ave., Kyiv 03680, Ukraine
| | - Uliana Afonina
- The Department of Physics of biological systems, Institute of Physics, NAS of Ukraine, 46 Nauky Ave., Kyiv 03680, Ukraine
| | - Kyrylo Pyrshev
- The Department of Neurochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, 9 Leontovicha Str., Kyiv 01054, Ukraine
| | - Galina Dovbeshko
- The Department of Physics of biological systems, Institute of Physics, NAS of Ukraine, 46 Nauky Ave., Kyiv 03680, Ukraine
| | - Semen Yesylevskyy
- The Department of Physics of biological systems, Institute of Physics, NAS of Ukraine, 46 Nauky Ave., Kyiv 03680, Ukraine; Laboratoire Chrono Environnement UMR CNRS 6249, Université de Bourgogne Franche-Comté, 16 route de Gray, 25030 Besançon Cedex, France
| | - Tatiana Borisova
- The Department of Neurochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, 9 Leontovicha Str., Kyiv 01054, Ukraine.
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Ferreira-da-Silva R, Ribeiro-Vaz I, Morato M, Junqueira Polónia J. A comprehensive review of adverse events to drugs used in COVID-19 patients: Recent clinical evidence. Eur J Clin Invest 2022; 52:e13763. [PMID: 35224719 PMCID: PMC9111855 DOI: 10.1111/eci.13763] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 02/16/2022] [Accepted: 02/20/2022] [Indexed: 01/08/2023]
Abstract
BACKGROUND Since the breakthrough of the pandemic, several drugs have been used to treat COVID-19 patients. This review aims to gather information on adverse events (AE) related to most drugs used in this context. METHODS We performed a literature search to find articles that contained information about AE in COVID-19 patients. We analysed and reviewed the most relevant studies in the Medline (via PubMed), Scopus and Web of Science. The most frequent AE identified were grouped in our qualitative analysis by System Organ Class (SOC), the highest level of the MedDRA medical terminology for each of the drugs studied. RESULTS The most frequent SOCs among the included drugs are investigations (n = 7 drugs); skin and subcutaneous tissue disorders (n = 5 drugs); and nervous system disorders, infections and infestations, gastrointestinal disorders, hepatobiliary disorders, and metabolism and nutrition disorders (n = 4 drugs). Other SOCs also emerged, such as general disorders and administration site conditions, renal and urinary disorders, vascular disorders and cardiac disorders (n = 3 drugs). Less frequent SOC were eye disorders, respiratory, thoracic and mediastinal disorders, musculoskeletal and connective tissue disorders, and immune system disorders (n = 2 drugs). Psychiatric disorders, and injury, poisoning and procedural complications were also reported (n = 1 drug). CONCLUSIONS Some SOCs seem to be more frequent than others among the COVID-19 drugs included, although neither of the studies included reported causality analysis. For that purpose, further clinical studies with robust methodologies, as randomised controlled trials, should be designed and performed.
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Affiliation(s)
- Renato Ferreira-da-Silva
- Porto Pharmacovigilance Centre, INFARMED, I.P, University of Porto, Porto, Portugal.,Department of Community Medicine, Health Information and Decision, University of Porto, Porto, Portugal.,CINTESIS - Center for Health Technology and Services Research, Porto, Portugal
| | - Inês Ribeiro-Vaz
- Porto Pharmacovigilance Centre, INFARMED, I.P, University of Porto, Porto, Portugal.,Department of Community Medicine, Health Information and Decision, University of Porto, Porto, Portugal.,CINTESIS - Center for Health Technology and Services Research, Porto, Portugal
| | - Manuela Morato
- LAQV/REQUIMTE, Laboratory of Pharmacology, Department of Drug Sciences, University of Porto, Porto, Portugal
| | - Jorge Junqueira Polónia
- Porto Pharmacovigilance Centre, INFARMED, I.P, University of Porto, Porto, Portugal.,CINTESIS - Center for Health Technology and Services Research, Porto, Portugal.,Department of Medicine, University of Porto, Porto, Portugal
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Boadu A, Agoni C, Karpoormath R, Soliman M, Nlooto M. Repurposing antiviral phytochemicals from the leaf extracts of Spondias mombin (Linn) towards the identification of potential SARSCOV-2 inhibitors. Sci Rep 2022; 12:10896. [PMID: 35764663 PMCID: PMC9240089 DOI: 10.1038/s41598-022-14558-3] [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: 10/21/2021] [Accepted: 06/08/2022] [Indexed: 11/30/2022] Open
Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a pneumonia-like disease with a pattern of acute respiratory symptoms, currently remains a significant public health concern causing tremendous human suffering. Although several approved vaccines exist, vaccine hesitancy, limited vaccine availability, high rate of viral mutation, and the absence of approved drugs account for the persistence of SARS-CoV-2 infections. The investigation of possibly repurposing of phytochemical compounds as therapeutic alternatives has gained momentum due to their reported affordability and minimal toxicity. This study investigated anti-viral phytochemical compounds from ethanolic leaf extracts of Spondias mombin L as potential inhibitor candidates against SARS-CoV-2. We identified Geraniin and 2-O-Caffeoyl-(+)-allohydroxycitric acid as potential SARS-CoV-2 inhibitor candidates targeting the SARS-CoV-2 RNA-dependent polymerase receptor-binding domain (RBD) of SARS-CoV-2 viral S-protein and the 3C-like main protease (3CLpro). Geraniin exhibited binding free energy (ΔGbind) of - 25.87 kcal/mol and - 21.74 kcal/mol towards SARS-CoV-2 RNA-dependent polymerase and receptor-binding domain (RBD) of SARS-CoV-2 viral S-protein respectively, whereas 2-O-Caffeoyl-(+)-allohydroxycitric acid exhibited a ΔGbind of - 32 kcal/mol towards 3CLpro. Molecular Dynamics simulations indicated a possible interference to the functioning of SARS-CoV-2 targets by the two identified inhibitors. However, further in vitro and in vivo evaluation of these potential SARS-CoV-2 therapeutic inhibitor candidates is needed.
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Affiliation(s)
- Akwasi Boadu
- Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, 4000, South Africa.
- Synthetic and Medicinal Chemistry Research Group (SMCRG), Department of Pharmaceutical Chemistry, Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, 4000, South Africa.
| | - Clement Agoni
- Molecular Bio-Computation and Drug Design Laboratory, School of Health Sciences, Discipline of Pharmaceutical Sciences, University of KwaZulu-Natal, KwaZulu-Natal, South Africa
| | - Rajshekhar Karpoormath
- Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, 4000, South Africa
- Synthetic and Medicinal Chemistry Research Group (SMCRG), Department of Pharmaceutical Chemistry, Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, 4000, South Africa
| | - Mahmoud Soliman
- Molecular Bio-Computation and Drug Design Laboratory, School of Health Sciences, Discipline of Pharmaceutical Sciences, University of KwaZulu-Natal, KwaZulu-Natal, South Africa
| | - Manimbulu Nlooto
- Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, 4000, South Africa
- Department of Pharmacy, School of Health Care Sciences, University of Limpopo, Private Bag X1106, Polokwane, Sovenga, 0727, South Africa
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30
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Ahmed Shawki M, Ali Sabri N, Mohamed Ibrahim D, Maged Samady M, Samir Hamza M, Samir Hamza M. "The Impact of Clinical Pharmacist Implemented Education on the Incidence of Prescribing Errors in COVID-19 patients". Saudi Pharm J 2022; 30:1101-1106. [PMID: 35719834 PMCID: PMC9197561 DOI: 10.1016/j.jsps.2022.06.007] [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: 07/14/2021] [Accepted: 06/11/2022] [Indexed: 10/28/2022] Open
Abstract
Background Clinical pharmacists have a vital role during COVID-19 pandemic in mitigating medication errors, particularly prescribing errors in hospitals. That is owing to the fact that prescribing errors during the COVID-19 pandemic has increased. Aim This study aimed to evaluate the impact of the clinical pharmacist on the rate of prescribing errors on COVID-19 patients in a governmental hospital. Methods The study was a pre-post study conducted from March 2020 till September 2020. It included the pre-education phase P0; a retrospective phase where all the prescription for COVID-19 patients were revised by the clinical pharmacy team and prescription errors were extracted. Followed by a one-month period; the clinical pharmacy team prepared educational materials in the form of posters and flyers covering all prescribing errors detected to be delivered to physicians. Then, the post-education phase P1; all prescriptions were monitored by the clinical pharmacy team to assess the rate and types of prescribing errors and the data extracted was compared to that from pre-education phase. Results The number of prescribing errors in P0 phase was 1054 while it was only 148 in P1 Phase. The clinical pharmacy team implemented education phase helped to significantly reduce the prescribing errors from 14.7/1000 patient-days in the P0 phase to 2.56 /1000 patient-days in the P1 phase (p-value <0.001). Conclusion The clinical pharmacist significantly reduced the rate of prescribing errors in patients with COVID-19 which emphasizes the great role of clinical pharmacists' interventions in the optimization of prescribing in these stressful conditions.
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Affiliation(s)
- May Ahmed Shawki
- Clinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Nagwa Ali Sabri
- Clinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | | | - Mohamed Maged Samady
- MSc degree of Hospital Management and Logistics, General Manager of New Cairo Hospital, Cairo, Egypt
| | - Marwa Samir Hamza
- Clinical Pharmacy Practice Department, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo, Egypt
| | - Marwa Samir Hamza
- Clinical Pharmacy Practice Department, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo, Egypt
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Testino G, Vignoli T, Patussi V, Allosio P, Amendola MF, Aricò S, Baselice A, Balbinot P, Campanile V, Fanucchi T, Greco G, Macciò L, Meneguzzi C, Mioni D, Palmieri VO, Parisi M, Renzetti D, Rossin R, Gandin C, Bottaro LC, Bernardi M, Addolorato G, Lungaro L, Zoli G, Scafato E, Caputo F. Alcohol-Related Liver Disease in the Covid-19 Era: Position Paper of the Italian Society on Alcohol (SIA). Dig Dis Sci 2022; 67:1975-1986. [PMID: 34142284 PMCID: PMC8210966 DOI: 10.1007/s10620-021-07006-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 04/14/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND Coronavirus Disease 2019 (COVID-19), firstly reported in China last November 2019, became a global pandemic. It has been shown that periods of isolation may induce a spike in alcohol use disorder (AUD). In addition, alcohol-related liver disease (ALD) is the most common consequence of excessive alcohol consumption worldwide. Moreover, liver impairment has also been reported as a common manifestation of COVID-19. AIMS The aim of our position paper was to consider some critical issues regarding the management of ALD in patients with AUD in the era of COVID-19. METHODS A panel of experts of the Italian Society of Alcohology (SIA) met via "conference calls" during the lockdown period to draft the SIA's criteria for the management of ALD in patients with COVID-19 as follows: (a) liver injury in patients with ALD and COVID-19 infection; (b) toxicity to the liver of the drugs currently tested to treat COVID-19 and the pharmacological interaction between medications used to treat AUD and to treat COVID-19; (c) reorganization of the management of compensated and decompensated ALD and liver transplantation in the COVID-19 era. RESULTS AND CONCLUSIONS The COVID-19 pandemic has rapidly carried us toward a new governance scenario of AUD and ALD which necessarily requires an in-depth review of the management of these diseases with a new safe approach (management of out-patients and in-patients following new rules of safety, telemedicine, telehealth, call meetings with clinicians, nurses, patients, and caregivers) without losing the therapeutic efficacy of multidisciplinary treatment.
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Affiliation(s)
- Gianni Testino
- Unit of Addiction and Hepatology, Regional Centre On Alcohol, ASL3 San Martino Hospital, Genova, Italy
| | - Teo Vignoli
- Unit of Addiction Treatment, Lugo, RA, Italy
| | | | | | | | - Sarino Aricò
- Gastroenterology Unit, Mauriziano Hospital, Torino, Italy
| | | | - Patrizia Balbinot
- Unit of Addiction and Hepatology, Regional Centre On Alcohol, ASL3 San Martino Hospital, Genova, Italy
| | | | | | | | | | | | | | - Vincenzo Ostilio Palmieri
- "Murri" Clinic of Internal Medicine, Department of Biomedical Science and Human Oncology, University of Bari, Bari, Italy
| | | | - Doda Renzetti
- Department of Internal Medicine, Mater Dei Hospital, Bari, Italy
| | | | - Claudia Gandin
- National Observatory On Alcohol, National Institute of Health, Roma, Italy
| | | | - Mauro Bernardi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Giovanni Addolorato
- Alcohol Use Disorder and Alcohol Related Disease Unit, Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Lisa Lungaro
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
| | - Giorgio Zoli
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
- Department of Internal Medicine, SS Annunziata Hospital, University of Ferrara, Via Vicini 2, 44042, Cento, FE, Italy
- Centre for the Study and Treatment of Alcohol-Related Diseases, Department of Translational Medicine, University of Ferrara, Ferrara, Italy
| | - Emanuele Scafato
- National Observatory On Alcohol, National Institute of Health, Roma, Italy
| | - Fabio Caputo
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy.
- Department of Internal Medicine, SS Annunziata Hospital, University of Ferrara, Via Vicini 2, 44042, Cento, FE, Italy.
- Centre for the Study and Treatment of Alcohol-Related Diseases, Department of Translational Medicine, University of Ferrara, Ferrara, Italy.
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Frequently Used Allopathic and Traditional Medicine for COVID-19 Treatment and Feasibility of Their Integration. Chin J Integr Med 2022; 28:1040-1047. [PMID: 35507298 PMCID: PMC9065245 DOI: 10.1007/s11655-021-3512-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/28/2021] [Indexed: 02/06/2023]
Abstract
To date, no satisfactory treatment for COVID-19 is available. This review reported few recent updates regarding the drugs (allopathy/traditional medicines) used for the treatment of COVID-19 concerning clinical studies. Content of the article spotlight the contribution of allopathic and Ayurvedic drugs to the scientific basis for utilization as a potential therapy against COVID-19 infection and provide new insights on the integration of allopathy and traditional medicine. It advocated the combination of these two systems of treatment will ascertain their integrations, and there would be a good possibility and scope for developing a model of integration in the management of COVID-19. Provided discussion may help researchers, physicians, and healthcare policymakers to encourage for effective and integrated use of allopathic and Ayurvedic medicines to control the COVID-19 pandemic more effectively.
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Kariyawasam JC, Jayarajah U, Abeysuriya V, Riza R, Seneviratne SL. Involvement of the Liver in COVID-19: A Systematic Review. Am J Trop Med Hyg 2022; 106:1026-1041. [PMID: 35203056 PMCID: PMC8991364 DOI: 10.4269/ajtmh.21-1240] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 01/16/2022] [Indexed: 01/11/2023] Open
Abstract
COVID-19, a respiratory viral infection, has affected 388 million individuals worldwide as of the February 4, 2022. In this review, we have outlined the important liver manifestations of COVID-19 and discussed the possible underlying pathophysiological mechanisms and their diagnosis and management. Factors that may contribute to hepatic involvement in COVID-19 include direct viral cytopathic effects, exaggerated immune responses/systemic inflammatory response syndrome, hypoxia-induced changes, vascular changes due to coagulopathy, endothelitis, cardiac congestion from right heart failure, and drug-induced liver injury. The majority of COVID-19-associated liver symptoms are mild and self-limiting. Thus management is generally supportive. Liver function tests and abdominal imaging are the primary investigations done in relation to liver involvement in COVID-19 patients. However, imaging findings are nonspecific. Severe acute respiratory syndrome coronavirus 2 RNA has been found in liver biopsies. However, there is limited place for liver biopsy in the clinical context, as it does not influence management. Although, the management is supportive in the majority of patients without previous liver disease, special emphasis is needed in those with nonalcoholic fatty liver disease, cirrhosis, hepatocellular carcinoma, hepatitis B and C infections, and alcoholic liver disease, and in liver transplant recipients.
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Affiliation(s)
| | - Umesh Jayarajah
- Postgraduate Institute of Medicine, University of Colombo, Colombo, Sri Lanka
| | - Visula Abeysuriya
- Nawaloka Hospital Research and Education Foundation, Nawaloka Hospitals, Colombo, Sri Lanka
| | - Rishdha Riza
- Colombo South Teaching Hospital, Colombo, Sri Lanka
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Xiang R, Yu Z, Wang Y, Wang L, Huo S, Li Y, Liang R, Hao Q, Ying T, Gao Y, Yu F, Jiang S. Recent advances in developing small-molecule inhibitors against SARS-CoV-2. Acta Pharm Sin B 2022; 12:1591-1623. [PMID: 34249607 PMCID: PMC8260826 DOI: 10.1016/j.apsb.2021.06.016] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Revised: 06/13/2021] [Accepted: 06/23/2021] [Indexed: 02/07/2023] Open
Abstract
The COVID-19 pandemic caused by the novel SARS-CoV-2 virus has caused havoc across the entire world. Even though several COVID-19 vaccines are currently in distribution worldwide, with others in the pipeline, treatment modalities lag behind. Accordingly, researchers have been working hard to understand the nature of the virus, its mutant strains, and the pathogenesis of the disease in order to uncover possible drug targets and effective therapeutic agents. As the research continues, we now know the genome structure, epidemiological and clinical features, and pathogenic mechanism of SARS-CoV-2. Here, we summarized the potential therapeutic targets involved in the life cycle of the virus. On the basis of these targets, small-molecule prophylactic and therapeutic agents have been or are being developed for prevention and treatment of SARS-CoV-2 infection.
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Affiliation(s)
- Rong Xiang
- College of Life Sciences, Hebei Agricultural University, Baoding 071001, China
| | - Zhengsen Yu
- College of Life Sciences, Hebei Agricultural University, Baoding 071001, China
| | - Yang Wang
- College of Life Sciences, Hebei Agricultural University, Baoding 071001, China
| | - Lili Wang
- Research Center of Chinese Jujube, Hebei Agricultural University, Baoding 071001, China
| | - Shanshan Huo
- College of Life Sciences, Hebei Agricultural University, Baoding 071001, China
| | - Yanbai Li
- College of Life Sciences, Hebei Agricultural University, Baoding 071001, China
| | - Ruiying Liang
- College of Life Sciences, Hebei Agricultural University, Baoding 071001, China
| | - Qinghong Hao
- College of Life Sciences, Hebei Agricultural University, Baoding 071001, China
| | - Tianlei Ying
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai 200032, China
| | - Yaning Gao
- Beijing Pharma and Biotech Center, Beijing 100176, China,Corresponding authors. Tel.: +86 21 54237673, fax: +86 21 54237465 (Shibo Jiang); Tel.: +86 312 7528935, fax: +86 312 7521283 (Fei Yu); Tel.: +86 10 62896868; fax: +86 10 62899978, (Yanning Gao).
| | - Fei Yu
- College of Life Sciences, Hebei Agricultural University, Baoding 071001, China,Corresponding authors. Tel.: +86 21 54237673, fax: +86 21 54237465 (Shibo Jiang); Tel.: +86 312 7528935, fax: +86 312 7521283 (Fei Yu); Tel.: +86 10 62896868; fax: +86 10 62899978, (Yanning Gao).
| | - Shibo Jiang
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai 200032, China,Corresponding authors. Tel.: +86 21 54237673, fax: +86 21 54237465 (Shibo Jiang); Tel.: +86 312 7528935, fax: +86 312 7521283 (Fei Yu); Tel.: +86 10 62896868; fax: +86 10 62899978, (Yanning Gao).
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Belleudi V, Finocchietti M, Fortinguerra F, Di Filippo A, Trotta F, Davoli M, Addis A. Drug Prescriptions in the Outpatient Management of COVID-19: Evidence-Based Recommendations Versus Real Practice. Front Pharmacol 2022; 13:825479. [PMID: 35401220 PMCID: PMC8988061 DOI: 10.3389/fphar.2022.825479] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 02/14/2022] [Indexed: 11/29/2022] Open
Abstract
Background: Evidence-based recommendations for outpatient management of COVID-19 were published by the Italian Medicines Agency (AIFA) to limit the use of off-label treatments. The aim of this study is to measure the use of outpatient drug treatments in a COVID-19-positive population, taking into account the Italian regulatory agency’s advices. Methods: A descriptive observational study was conducted. All patients testing positive for COVID-19 residing in Lazio region, Italy, with diagnosis date between March 2020 and May 2021 were selected, and outpatient medicine prescription patterns were identified. Results: Independent of AIFA recommendations, the use of drug therapy in the management of outpatient COVID-19 cases was frequent (about one-third of the cases). The most used drug therapy was antibiotics, specifically azithromycin, despite the negative recommendation of AIFA, while the use of corticosteroids increased after the positive recommendation of regulatory agency for the use in subjects with severe COVID-19 disease. The use of hydroxychloroquine was limited to the early pandemic period where evidence on its potential benefit was controversial. Antithrombotics were widely used in outpatient settings, even if their use was recommended for hospitalized patients. Conclusion: In this study, we show a frequent use of drug therapy in the management of outpatient cases of COVID-19, mainly attributable to antibiotics use. Our research highlights the discrepancy between recommendations for care and clinical practice and the need for strategies to bridge gaps in evidence-informed decision-making.
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Affiliation(s)
- Valeria Belleudi
- Department of Epidemiology, Lazio Regional Health Service, Rome, Italy
- *Correspondence: Valeria Belleudi,
| | | | | | | | | | - Marina Davoli
- Department of Epidemiology, Lazio Regional Health Service, Rome, Italy
| | - Antonio Addis
- Department of Epidemiology, Lazio Regional Health Service, Rome, Italy
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Gao S, Yang Q, Wang X, Hu W, Lu Y, Yang K, Jiang Q, Li W, Song H, Sun F, Cheng H. Association Between Drug Treatments and the Incidence of Liver Injury in Hospitalized Patients With COVID-19. Front Pharmacol 2022; 13:799338. [PMID: 35387350 PMCID: PMC8978013 DOI: 10.3389/fphar.2022.799338] [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: 10/21/2021] [Accepted: 02/28/2022] [Indexed: 01/08/2023] Open
Abstract
The outbreak of coronavirus disease 2019 (COVID-19) has led to the emergence of global health care. In this study, we aimed to explore the association between drug treatments and the incidence of drug-induced liver injury (DILI) in hospitalized patients with COVID-19. A retrospective study was conducted on 5113 COVID-19 patients in Hubei province, among which 395 incurred liver injury. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards models. The results showed that COVID-19 patients who received antibiotics (HR 1.97, 95% CI: 1.55-2.51, p < 0.001), antifungal agents (HR 3.10, 95% CI: 1.93-4.99, p < 0.001) and corticosteroids (HR 2.31, 95% CI: 1.80-2.96, p < 0.001) had a higher risk of DILI compared to non-users. Special attention was given to the use of parenteral nutrition (HR 1.82, 95% CI: 1.31-2.52, p < 0.001) and enteral nutrition (HR 2.71, 95% CI: 1.98-3.71, p < 0.001), which were the risk factors for liver injury. In conclusion, this study suggests that the development of DILI in hospitalized patients with COVID-19 needs to be closely monitored, and the above-mentioned drug treatments may contribute to the risk of DILI.
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Affiliation(s)
- Suyu Gao
- Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Qingqing Yang
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Xuanxuan Wang
- Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Wen Hu
- Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Yun Lu
- Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Kun Yang
- Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Qiaoli Jiang
- Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Wenjing Li
- Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Haibo Song
- Key Laboratory for Research and Evaluation of Pharmacovigilance, National Medical Products Administration, Beijing, China
- Chinese Society of Toxicology, Beijing, China
| | - Feng Sun
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Hong Cheng
- Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, China
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Islam MA, Haque MA, Rahman MA, Hossen F, Reza M, Barua A, Marzan AA, Das T, Kumar Baral S, He C, Ahmed F, Bhattacharya P, Jakariya M. A Review on Measures to Rejuvenate Immune System: Natural Mode of Protection Against Coronavirus Infection. Front Immunol 2022; 13:837290. [PMID: 35371007 PMCID: PMC8965011 DOI: 10.3389/fimmu.2022.837290] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Accepted: 02/21/2022] [Indexed: 01/18/2023] Open
Abstract
SARS-CoV-2, a novel Corona virus strain, was first detected in Wuhan, China, in December 2019. As of December 16, 2021, almost 4,822,472 people had died and over 236,132,082 were infected with this lethal viral infection. It is believed that the human immune system is thought to play a critical role in the initial phase of infection when the viruses invade the host cells. Although some effective vaccines have already been on the market, researchers and many bio-pharmaceuticals are still working hard to develop a fully functional vaccine or more effective therapeutic agent against the COVID-19. Other efforts, in addition to functional vaccines, can help strengthen the immune system to defeat the corona virus infection. Herein, we have reviewed some of those proven measures, following which a more efficient immune system can be better prepared to fight viral infection. Among these, dietary supplements like- fresh vegetables and fruits offer a plentiful of vitamins and antioxidants, enabling to build of a healthy immune system. While the pharmacologically active components of medicinal plants directly aid in fighting against viral infection, supplementary supplements combined with a healthy diet will assist to regulate the immune system and will prevent viral infection. In addition, some personal habits, like- regular physical exercise, intermittent fasting, and adequate sleep, had also been proven to aid the immune system in becoming an efficient one. Maintaining each of these will strengthen the immune system, allowing innate immunity to become a more defensive and active antagonistic mechanism against corona-virus infection. However, because dietary treatments take longer to produce beneficial effects in adaptive maturation, personalized nutrition cannot be expected to have an immediate impact on the global outbreak.
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Affiliation(s)
- Md. Aminul Islam
- Department of Microbiology, Noakhali Science and Technology University, Noakhali, Bangladesh
- Department of Microbiology President Abdul Hamid Medical College, Karimganj, Bangladesh
| | - Md. Atiqul Haque
- Key Lab of Animal Epidemiology and Zoonoses of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing, China
- Department of Microbiology, Faculty of Veterinary and Animal Science, Hajee Mohammad Danesh Science and Technology University, Dinajpur, Bangladesh
| | - Md. Arifur Rahman
- Department of Microbiology, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Foysal Hossen
- Department of Microbiology, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Mahin Reza
- Department of Microbiology, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Abanti Barua
- Department of Microbiology, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Abdullah Al Marzan
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, Bangladesh
| | - Tuhin Das
- Department of Microbiology, University of Chittagong, Chittagong, Bangladesh
| | | | - Cheng He
- Key Lab of Animal Epidemiology and Zoonoses of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Firoz Ahmed
- Department of Microbiology, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Prosun Bhattacharya
- COVID-19 Research@KTH, Department of Sustainable Development, Environmental Science and Engineering, KTH Royal Institute of Technology, Stockholm, Sweden
| | - Md. Jakariya
- Department of Environmental Science and Management, North South University, Dhaka, Bangladesh
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Ashour NA, Abo Elmaaty A, Sarhan AA, Elkaeed EB, Moussa AM, Erfan IA, Al-Karmalawy AA. A Systematic Review of the Global Intervention for SARS-CoV-2 Combating: From Drugs Repurposing to Molnupiravir Approval. Drug Des Devel Ther 2022; 16:685-715. [PMID: 35321497 PMCID: PMC8935998 DOI: 10.2147/dddt.s354841] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 02/26/2022] [Indexed: 02/05/2023] Open
Abstract
The rising outbreak of SARS-CoV-2 continues to unfold all over the world. The development of novel effective antiviral drugs to fight against SARS-CoV-2 is a time cost. As a result, some specific FDA-approved drugs have already been repurposed and authorized for COVID-19 treatment. The repurposed drugs used were either antiviral or non-antiviral drugs. Accordingly, the present review thoroughly focuses on the repurposing efficacy of these drugs including clinical trials experienced, the combination therapies used, the novel methods followed for treatment, and their future perspective. Therefore, drug repurposing was regarded as an effective avenue for COVID-19 treatment. Recently, molnupiravir is a prodrug antiviral medication that was approved in the United Kingdom in November 2021 for the treatment of COVID-19. On the other hand, PF-07321332 is an oral antiviral drug developed by Pfizer. For the treatment of COVID-19, the PF-07321332/ritonavir combination medication is used in Phase III studies and was marketed as Paxlovid. Herein, we represented the almost history of combating COVID-19 from repurposing to the recently available oral anti-SARS-CoV-2 candidates, as a new hope to end the current pandemic.
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Affiliation(s)
- Nada A Ashour
- Department of Clinical Pharmacology, Faculty of Pharmacy, Horus University-Egypt, New Damietta, 34518, Egypt
| | - Ayman Abo Elmaaty
- Department of Medicinal Chemistry, Faculty of Pharmacy, Port Said University, Port Said, 42526, Egypt
| | - Amany A Sarhan
- Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta, 34518, Egypt
| | - Eslam B Elkaeed
- Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Ad Diriyah, 13713, Riyadh, Saudi Arabia
| | - Ahmed M Moussa
- Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta, 34518, Egypt
| | - Ibrahim Ali Erfan
- Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta, 34518, Egypt
| | - Ahmed A Al-Karmalawy
- Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta, 34518, Egypt
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Yun SH, Park BG, Jung EY, Kwon JY, Park YK, Kim HJ. Factors Affecting the Practice of Corona Virus Disease-19 Prevention Activities in Patients With Heart Diseases in Korea. Clin Nurs Res 2022; 31:713-723. [PMID: 35164575 DOI: 10.1177/10547738211068140] [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: 01/08/2023]
Abstract
This study was conducted in a cross-sectional correlation design to identify factors affecting the practice of COVID-19 prevention activities in patients with heart diseases. A convenience sample of 195 patients with heart diseases from one tertiary teaching hospital completed questionnaires with items from the characteristics of these participants, their knowledge, attitude, and practice related to COVID-19 prevention activities. Participants' knowledge, attitude, and practice for COVID-19 prevention were relatively high but there was a significant difference in the degree of practice of COVID-19 prevention activities according to the characteristics of the participants. The higher the level of their knowledge and the more positive their attitude, the higher their practice. Attitude and information check about COVID-19 prevention were factors that influenced the practice of COVID-19 prevention activities, with an explanatory power of 32%. This study can help motivate and actively encourage COVID-19 prevention practices.
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Affiliation(s)
- Sun-Hee Yun
- The Catholic University of Korea, Seoul, Republic of Korea
| | - Byung-Gyu Park
- The Catholic University of Korea, Seoul, Republic of Korea
| | - Eun-Young Jung
- The Catholic University of Korea, Seoul, Republic of Korea
| | - Ji-Yeon Kwon
- The Catholic University of Korea, Seoul, Republic of Korea
| | | | - Hea-Jeong Kim
- The Catholic University of Korea, Seoul, Republic of Korea
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Niazi S, Niazi F, Doroodgar F, Safi M. The Cardiac Effects of COVID-19: Review of articles. Curr Probl Cardiol 2022; 47:100981. [PMID: 34534589 PMCID: PMC8438797 DOI: 10.1016/j.cpcardiol.2021.100981] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 08/13/2021] [Accepted: 09/03/2021] [Indexed: 01/08/2023]
Abstract
Cardiovascular wellbeing has been dramatically affected by severe acute respiratory syndrome coronavirus (SARS-CoV-2), the reason for the coronavirus disease pandemic 2019 (COVID-19) pandemic. There is a greater risk of morbidity and death in individuals with preexisting heart diseases. Clinical syndromes of the acute coronary syndrome, acute myocardial injury, myocarditis, arrhythmias, heart failure, and venous thromboembolism can, directly and indirectly, affect the heart. There may also be adverse heart effects of specific therapeutics under review for COVID-19. The renin-angiotensin-aldosterone system (RAAS) mechanism in virus replication makes it essential to understand the consequences of the system-modulating medications. For optimum patient care, detailed knowledge of specific cardiovascular symptoms of COVID-19 and the role of RAAS in the prognosis of COVID-19 disease is necessary.
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Affiliation(s)
- Sana Niazi
- Medical Students Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Feizollah Niazi
- Research Center of Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farideh Doroodgar
- Negah Specialty Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Morteza Safi
- Cardiovascular Research Center of Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Shoukat H, Pervaiz F, Rehman S. Pluronic F127-co-poly (2 acrylamido-2-methylpropane sulphonic acid) crosslinked matrices as potential controlled release carrier for an anti-depressant drug: in vitro and in vivo attributes. CHEMICAL PAPERS 2022. [DOI: 10.1007/s11696-022-02077-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Sahoo BM, Bhattamisra SK, Das S, Tiwari A, Tiwari V, Kumar M, Singh S. Computational Approach to Combat COVID-19 Infection: Emerging Tool for Accelerating Drug Research. Curr Drug Discov Technol 2022; 19:e170122200314. [PMID: 35040405 DOI: 10.2174/1570163819666220117161308] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 10/05/2021] [Accepted: 10/11/2021] [Indexed: 01/08/2023]
Abstract
BACKGROUND Drug discovery and development process is an expensive, complex, time-consuming and risky. There are different techniques involved in the drug development process which include random screening, computational approach, molecular manipulation and serendipitous research. Among these methods, the computational approach is considered as an efficient strategy to accelerate and economize the drug discovery process. OBJECTIVE This approach is mainly applied in various phases of drug discovery process including target identification, target validation, lead identification and lead optimization. Due to increase in the availability of information regarding various biological targets of different disease states, computational approaches such as molecular docking, de novo design, molecular similarity calculation, virtual screening, pharmacophore-based modeling and pharmacophore mapping have been applied extensively. METHODS Various drug molecules can be designed by applying computational tools to explore the drug candidates for treatment of Coronavirus infection. The world health organization has announced the novel corona virus disease as COVID-19 and declared it as pandemic globally on 11 February 2020. So, it is thought of interest to scientific community to apply computational methods to design and optimize the pharmacological properties of various clinically available and FDA approved drugs such as remdesivir, ribavirin, favipiravir, oseltamivir, ritonavir, arbidol, chloroquine, hydroxychloroquine, carfilzomib, baraticinib, prulifloxacin, etc for effective treatment of COVID-19 infection. RESULTS Further, various survey reports suggest that the extensive studies are carried out by various research communities to find out the safety and efficacy profile of these drug candidates. CONCLUSION This review is focused on the study of various aspects of these drugs related to their target sites on virus, binding interactions, physicochemical properties etc.
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Affiliation(s)
- Biswa Mohan Sahoo
- Roland Institute of Pharmaceutical Sciences, Berhampur-760010, Odisha, India
| | - Subrat Kumar Bhattamisra
- Department of Pharmaceutical Technology, School of Medical Sciences, Adamas University, Jagannathpur, Kolkata-700126, West Bengal, India
| | - Sarita Das
- Microbiology Laboratory, Department of Botany, Berhampur University, Bhanja Bihar, Berhampur- 760007, Odisha, India
| | - Abhishek Tiwari
- Devasthali Vidyapeeth College of Pharmacy, Lalpur, Rudrapur-263148, Uttarakhand, India
| | - Varsha Tiwari
- Devasthali Vidyapeeth College of Pharmacy, Lalpur, Rudrapur-263148, Uttarakhand, India
| | - Manish Kumar
- M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala-133207, Haryana, India
| | - Sunil Singh
- Shri Sai College of Pharmacy, Handia, Prayagraj, Uttar Pradesh, 221503, India
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Abdelsalam M, Abd El Wahab AM, Nassar MK, Samaan E, Eldeep A, Abdalbary M, Tawfik M, Saleh M, Shemies RS, Sabry A. Kidneys in SARS-CoV-2 Era; a challenge of multiple faces. Ther Apher Dial 2022; 26:552-565. [PMID: 34989119 DOI: 10.1111/1744-9987.13792] [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] [Received: 09/11/2021] [Revised: 12/31/2021] [Accepted: 01/03/2022] [Indexed: 01/08/2023]
Abstract
INTRODUCTION With the evolution of SARS-CoV-2 pandemic, it was believed to be a direct respiratory virus. But, its deleterious effects were observed on different body systems, including kidneys. AIM OF WORK In this review, we tried as much as we can to summarize what has been discussed in the literature about the relation between SARS-CoV-2 infection and kidneys since December, 2019. METHODS Each part of the review was assigned to one or two authors to search for relevant articles in three databases (Pubmed, Scopus and Google scholar) and collected data were summarized and revised by two independent researchers. CONCLUSION The complexity of COVID-19 pandemic and kidney could be attributed to the direct effect of SARS-CoV-2 infection on the kidneys, different clinical presentation, difficulties confronting dialysis patients, restrictions of the organ transplant programs, poor outcomes and bad prognosis in patients with known history of kidney diseases who got infected with SARS-CoV-2. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Mostafa Abdelsalam
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura, Egypt
| | | | | | - Emad Samaan
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura, Egypt
| | - Ahmed Eldeep
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura, Egypt
| | - Mohamed Abdalbary
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura, Egypt.,Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, US
| | - Mona Tawfik
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura, Egypt
| | - Marwa Saleh
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura, Egypt
| | | | - Alaa Sabry
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura, Egypt
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Computational approaches for drug repositioning and repurposing to combat SARS-CoV-2 infection. COMPUTATIONAL APPROACHES FOR NOVEL THERAPEUTIC AND DIAGNOSTIC DESIGNING TO MITIGATE SARS-COV-2 INFECTION 2022:247-265. [PMCID: PMC9300474 DOI: 10.1016/b978-0-323-91172-6.00008-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 05/11/2025]
Abstract
Drug repositioning (also referred to as drug repurposing) is the method of exploring novel therapeutic indications for Food and Drug Administration-approved clinically implemented drugs. The unique strategy of drug repositioning is used to boost the drug development process since drug discovery is an expensive, arduous, cumbersome, and high-risk procedure. Recently, several pharmaceutical firms have used the drug repositioning technique in their drug discovery and development programs to develop new medications based on the identification of new therapeutic targets. This technique is extremely effective, saves time, is comparatively economical, and has a low chance of failure. Developing appropriate treatment measures to inhibit the spread of Coronavirus disease-2019 (COVID-19) is currently a top priority. As a result, several studies were conducted to build novel therapeutic molecules using diverse strategies of drug repurposing to discover drug candidates against COVID-19 infection that can act as substantial inhibitors against virus particles. By implementing virtual screening of drug libraries, it is possible to identify potential drugs through drug repurposing. A molecular docking approach and calculation of binding free energy are used to estimate binding affinity and drug–receptor interactions. Drug-repurposing methodologies can be divided into three categories: target-oriented, drug-oriented, and disease-oriented, based on the gathered data about the various physicochemical, pharmacokinetic and pharmacological features of a drug candidate. Using computational methods such as homology modeling and molecular similarity, this methodology aids in determining the binding interaction of drug molecules with the target protein of the virus. In this book chapter, we explore a typical set of currently utilized computational techniques for identifying repurposable drug molecules for COVID-19, as well as their supporting databases. We also assess promising drugs anticipated by computational approaches to drugs currently being evaluated in clinical trials. Moreover, we also examine the takeaways from the evaluated research efforts, such as how to competently combine bioinformatics tools with experimental work and suggest a fully integrated drug-repurposing approach to combat the deadly COVID-19 infection.
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Plassmeyer M, Alpan O, Corley MJ, Premeaux TA, Lillard K, Coatney P, Vaziri T, Michalsky S, Pang APS, Bukhari Z, Yeung ST, Evering TH, Naughton G, Latterich M, Mudd P, Spada A, Rindone N, Loizou D, Ulrik Sønder S, Ndhlovu LC, Gupta R. Caspases and therapeutic potential of caspase inhibitors in moderate-severe SARS-CoV-2 infection and long COVID. Allergy 2022; 77:118-129. [PMID: 33993490 PMCID: PMC8222863 DOI: 10.1111/all.14907] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 04/21/2021] [Accepted: 04/22/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND COVID-19 can present with lymphopenia and extraordinary complex multiorgan pathologies that can trigger long-term sequela. AIMS Given that inflammasome products, like caspase-1, play a role in the pathophysiology of a number of co-morbid conditions, we investigated caspases across the spectrum of COVID-19 disease. MATERIALS & METHODS We assessed transcriptional states of multiple caspases and using flow cytometry, the expression of active caspase-1 in blood cells from COVID-19 patients in acute and convalescent stages of disease. Non-COVID-19 subject presenting with various comorbid conditions served as controls. RESULTS Single-cell RNA-seq data of immune cells from COVID-19 patients showed a distinct caspase expression pattern in T cells, neutrophils, dendritic cells, and eosinophils compared with controls. Caspase-1 was upregulated in CD4+ T-cells from hospitalized COVID-19 patients compared with unexposed controls. Post-COVID-19 patients with lingering symptoms (long-haulers) also showed upregulated caspase-1activity in CD4+ T-cells that ex vivo was attenuated with a select pan-caspase inhibitor. We observed elevated caspase-3/7levels in red blood cells from COVID-19 patients compared with controls that was reduced following caspase inhibition. DISCUSSION Our preliminary results suggest an exuberant caspase response in COVID-19 that may facilitate immune-related pathological processes leading to severe outcomes. Further clinical correlations of caspase expression in different stages of COVID-19 will be needed. CONCLUSION Pan-caspase inhibition could emerge as a therapeutic strategy to ameliorate or prevent severe COVID-19.
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Affiliation(s)
| | | | - Michael J. Corley
- Department of Medicine Division of Infectious Diseases Weill Cornell Medicine New York City NY USA
| | - Thomas A. Premeaux
- Department of Medicine Division of Infectious Diseases Weill Cornell Medicine New York City NY USA
| | | | | | | | | | - Alina P. S. Pang
- Department of Medicine Division of Infectious Diseases Weill Cornell Medicine New York City NY USA
| | - Zaheer Bukhari
- S.U.N.Y. Downstate Health Sciences University Brooklyn NY USA
| | - Stephen T. Yeung
- Department of Medicine Division of Infectious Diseases Weill Cornell Medicine New York City NY USA
| | - Teresa H. Evering
- Department of Medicine Division of Infectious Diseases Weill Cornell Medicine New York City NY USA
| | | | | | - Philip Mudd
- Department of Emergency Medicine Washington University School of Medicine Saint Louis MO USA
| | | | | | | | | | - Lishomwa C. Ndhlovu
- Department of Medicine Division of Infectious Diseases Weill Cornell Medicine New York City NY USA
| | - Raavi Gupta
- S.U.N.Y. Downstate Health Sciences University Brooklyn NY USA
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Baricitinib combination therapy: a narrative review of repurposed Janus kinase inhibitor against severe SARS-CoV-2 infection. Infection 2022; 50:295-308. [PMID: 34902115 PMCID: PMC8666469 DOI: 10.1007/s15010-021-01730-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 11/06/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE The Coronavirus disease 2019 (COVID-19) pandemic is one of the most devastating global problems. Regarding the lack of disease-specific treatments, repurposing drug therapy is currently considered a promising therapeutic approach in pandemic situations. Recently, the combination therapy of Janus kinase (JAK) inhibitor baricitinib has been authorized for emergency COVID-19 hospitalized patients; however, this strategy's safety, drug-drug interactions, and cellular signaling pathways remain a tremendous challenge. METHODS In this study, we aimed to provide a deep insight into the baricitinib combination therapies in severe COVID-19 patients through reviewing the published literature on PubMed, Scopus, and Google scholar databases. We also focused on cellular and subcellular pathways related to the synergistic effects of baricitinib plus antiviral agents, virus entry, and cytokine storm (CS) induction. The safety and effectiveness of this strategy have also been discussed in moderate to severe forms of COVID-19 infection. RESULTS The severity of COVID-19 is commonly associated with a dysregulated immune response and excessive release of pro-inflammatory agents, resulting in CS. It has been shown that baricitinib combined with antiviral agents could modulate the inflammatory response and provide a series of positive therapeutic outcomes in hospitalized adults and pediatric patients (age ≥ two years old). CONCLUSION Baricitinib plus the standard of care treatment might be a potential strategy in hospitalized patients with severe COVID-19.
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Law MF, Ho R, Law KWT, Cheung CKM. Gastrointestinal and hepatic side effects of potential treatment for COVID-19 and vaccination in patients with chronic liver diseases. World J Hepatol 2021; 13:1850-1874. [PMID: 35069994 PMCID: PMC8727202 DOI: 10.4254/wjh.v13.i12.1850] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 07/20/2021] [Accepted: 11/15/2021] [Indexed: 02/06/2023] Open
Abstract
The outbreak of coronavirus disease 2019 (COVID-19) is a global pandemic. Many clinical trials have been performed to investigate potential treatments or vaccines for this disease to reduce the high morbidity and mortality. The drugs of higher interest include umifenovir, bromhexine, remdesivir, lopinavir/ritonavir, steroid, tocilizumab, interferon alpha or beta, ribavirin, fivapiravir, nitazoxanide, ivermectin, molnupiravir, hydroxychloroquine/chloroquine alone or in combination with azithromycin, and baricitinib. Gastrointestinal (GI) symptoms and liver dysfunction are frequently seen in patients with COVID-19, which can make it difficult to differentiate disease manifestations from treatment adverse effects. GI symptoms of COVID-19 include anorexia, dyspepsia, nausea, vomiting, diarrhea and abdominal pain. Liver injury can be a result of systemic inflammation or cytokine storm, or due to the adverse drug effects in patients who have been receiving different treatments. Regular monitoring of liver function should be performed. COVID-19 vaccines have been rapidly developed with different technologies including mRNA, viral vectors, inactivated viruses, recombinant DNA, protein subunits and live attenuated viruses. Patients with chronic liver disease or inflammatory bowel disease and liver transplant recipients are encouraged to receive vaccination as the benefits outweigh the risks. Vaccination against COVID-19 is also recommended to family members and healthcare professionals caring for these patients to reduce exposure to the severe acute respiratory syndrome coronavirus 2 virus.
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Affiliation(s)
- Man Fai Law
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
| | - Rita Ho
- Department of Medicine, North District Hospital, Hong Kong, China
| | | | - Carmen Ka Man Cheung
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
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Kariyawasam JC, Jayarajah U, Riza R, Abeysuriya V, Seneviratne SL. Gastrointestinal manifestations in COVID-19. Trans R Soc Trop Med Hyg 2021; 115:1362-1388. [PMID: 33728439 PMCID: PMC7989191 DOI: 10.1093/trstmh/trab042] [Citation(s) in RCA: 87] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 02/15/2021] [Accepted: 02/18/2021] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19), a respiratory viral infection, has affected more than 78 million individuals worldwide as of the end of December 2020. Previous studies reported that severe acute respiratory syndrome coronavirus 1 and Middle East respiratory syndrome-related coronavirus infections may affect the gastrointestinal (GI) system. In this review we outline the important GI manifestations of COVID-19 and discuss the possible underlying pathophysiological mechanisms and their diagnosis and management. GI manifestations are reported in 11.4-61.1% of individuals with COVID-19, with variable onset and severity. The majority of COVID-19-associated GI symptoms are mild and self-limiting and include anorexia, diarrhoea, nausea, vomiting and abdominal pain/discomfort. A minority of patients present with an acute abdomen with aetiologies such as acute pancreatitis, acute appendicitis, intestinal obstruction, bowel ischaemia, haemoperitoneum or abdominal compartment syndrome. Severe acute respiratory syndrome coronavirus 2 RNA has been found in biopsies from all parts of the alimentary canal. Involvement of the GI tract may be due to direct viral injury and/or an inflammatory immune response and may lead to malabsorption, an imbalance in intestinal secretions and gut mucosal integrity and activation of the enteric nervous system. Supportive and symptomatic care is the mainstay of therapy. However, a minority may require surgical or endoscopic treatment for acute abdomen and GI bleeding.
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Affiliation(s)
- Jayani C Kariyawasam
- Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Colombo, Sri Lanka
| | - Umesh Jayarajah
- Postgraduate Institute of Medicine, University of Colombo, Colombo, Sri Lanka
| | - Rishdha Riza
- Colombo South Teaching Hospital, Colombo, Sri Lanka
| | - Visula Abeysuriya
- Nawaloka Hospital Research and Education Foundation, Nawaloka Hospitals, Colombo, Sri Lanka
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Sulewski A, Sieroń D, Szyluk K, Dąbrowski M, Kubaszewski Ł, Lukoszek D, Christe A. Avascular Necrosis Bone Complication after Active COVID-19 Infection: Preliminary Results. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:medicina57121311. [PMID: 34946256 PMCID: PMC8709043 DOI: 10.3390/medicina57121311] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 11/16/2021] [Accepted: 11/26/2021] [Indexed: 12/22/2022]
Abstract
Background and objectives: The course of SARS-CoV-2 (COVID-19) is still under analysis. The majority of complications arising from the infection are related to the respiratory system. The adverse effect of the viral infection on bone and joint tissue has also been observed. Materials and Methods: We present a group of 10 patients with degeneration of large joints and adjacent epiphyses of long bones and the spine, with a background of bone infarctions and avascular necrosis (AVN) immediately after infection with the COVID-19 virus. In MR imaging, changes in the characteristics of AVN were documented. Results: Observation of this group showed a clear correlation among the history of COVID-19 disease in the patients, moderately severe symptoms, high levels of IgG antibodies, and the time of occurrence of joint changes. No other clinically significant complications were observed following COVID-19 infection in the study group. No other risk factors for AVN or autoimmune or degenerative diseases were found in the study group. The group of patients responded well to empirical treatment with steroids, which normalized acute inflammatory symptoms and pain in the joints. Conclusions: During coronavirus (COVID-19) infection, there are complications in the locomotor system, such as microembolism and the formation of AVN; hence, more research is needed.
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Affiliation(s)
- Adam Sulewski
- Adult Spine Orthopaedics Department, Poznan University of Medical Sciences, 61545 Poznan, Poland; (M.D.); (Ł.K.)
- Correspondence:
| | - Dominik Sieroń
- Division of Magnetic Resonance Imaging, Silesian Center for Heart Diseases, 41800 Zabrze, Poland;
| | - Karol Szyluk
- Department of Physiotherapy, Faculty of Health Sciences in Katowice, Medical University of Silesia in Katowice, 40752 Katowice, Poland;
- I Department of Orthopaedic and Trauma Surgery, District Hospital of Orthopaedics and Trauma Surgery, Bytomska 62 Str., 41940 Piekary Śląskie, Poland
| | - Mikołaj Dąbrowski
- Adult Spine Orthopaedics Department, Poznan University of Medical Sciences, 61545 Poznan, Poland; (M.D.); (Ł.K.)
| | - Łukasz Kubaszewski
- Adult Spine Orthopaedics Department, Poznan University of Medical Sciences, 61545 Poznan, Poland; (M.D.); (Ł.K.)
| | - Dawid Lukoszek
- Dawid Lukoszek Physiotherapy Osteopathy, 42690 Hanusek, Poland;
| | - Andreas Christe
- Department of Radiology, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 10, 3010 Bern, Switzerland;
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Korkmaz İ, Keleş F. COVID-19-Related Lung Involvement at Different Time Intervals: Evaluation of Computed Tomography Images With Semiquantitative Scoring System and COVID-19 Reporting and Data System Scoring. Cureus 2021; 13:e18554. [PMID: 34765340 PMCID: PMC8575326 DOI: 10.7759/cureus.18554] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/06/2021] [Indexed: 12/21/2022] Open
Abstract
INTRODUCTION This study aimed to evaluate the frequency of typical and atypical thoracic CT findings in patient groups diagnosed during different periods of the pandemic, examine disease severity using radiological scoring methods, and determine the relationship between atypical CT findings and disease severity. MATERIALS AND METHODS One hundred fifty-one patients with positive reverse transcription polymerase chain reaction (RT-PCR) test and thoracic CT scan were included in the study. The patients were divided into two groups as group 1 (March to August 2020) diagnosed in the first six months of the pandemic and group 2 (September 2020 to February 2021) diagnosed in the second six months. CT images of the patients were analyzed for the frequency of typical and atypical findings. Evaluation was made in terms of disease suspicion and severity by scoring methods, and the relationship between atypical findings and disease severity was examined. RESULTS There was no statistically significant difference between the frequency and distribution patterns of typical CT findings observed in both groups. The most common atypical finding in both groups was nodular lesions. Central distribution, one of the atypical findings, was not seen in group 1, whereas it was present in nine patients in group 2 (p=0.001). The mean CT severity score was higher in group 2, and there was a statistically significant difference between the mean CT scores of both groups (p<0.001). In addition, six (7.2%) patients in group 1 and 34 (50%) patients in group 2 had CT scores above the cut-off value (p<0.001). There was no statistically significant relationship between atypical findings and severity score. CONCLUSION Other diseases and atypical findings that may accompany COVID-19 pneumonia may increase the rate of misdiagnosis. In the diagnosis of the disease, clinical signs and symptoms and radiological findings should be evaluated together, and it should be kept in mind that lung findings in thorax CT change over time.
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Affiliation(s)
- İnan Korkmaz
- Department of Radiology, Hatay Mustafa Kemal University, Faculty of Medicine, Antakya, TUR
| | - Fatma Keleş
- Department of Radiology, Hatay Mustafa Kemal University, Faculty of Medicine, Antakya, TUR
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