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Ketebchi S, Papari Moghadamfard M. A review on the effective natural compounds of medicinal plants on the COVID-19. Nat Prod Res 2025; 39:834-847. [PMID: 38333915 DOI: 10.1080/14786419.2024.2309322] [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: 04/15/2023] [Revised: 12/31/2023] [Accepted: 01/17/2024] [Indexed: 02/10/2024]
Abstract
In this review out of 300 selected articles 70 articles were evaluated, and the most significant compounds impacting COVID-19 and their mechanism of action were introduced. The compounds belong to four categories as follow: Phenolic, Flavonoid, Terpenoid, and Alkaloid compounds. In the phenol groups, the most effective compounds are scutellarin (suppressor of COVID-19 virus), thymol and carvacrol (the most inhibitory effect on COVID-19 virus), in the flavonoid groups, hesperdin (a strong inhibitor on COVID-19), in the terpenoids, methyl tanshinonate and sojil COVID-19 inhibitory effect) and 1,8-cineol (COVID-19 inhibitory effect) and in the last group, niglidine and quinoline alkaloid compounds (COVID-19 inhibitory effect) have been identified and introduced. These compounds have shown promising results due to their structure and effective mechanisms on COVID-19, so it can be an idea for researchers in this field to try to produce drugs by using natural compounds against the COVID-19 and Corona viruses.
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Affiliation(s)
- Saghar Ketebchi
- Department of Plant Pathology and Plant Protection (Microbiology), Shiraz Branch, Islamic Azad University, Shiraz, Iran
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2
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Alam K, Hossain MS, Zhao Y, Zhang Z, Xu S, Hao J, Yang Q, Li A. Tryptanthrins as multi-bioactive agents: discovery, diversity distribution and synthesis. Bioorg Chem 2025; 154:108071. [PMID: 39721143 DOI: 10.1016/j.bioorg.2024.108071] [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: 07/11/2024] [Revised: 12/08/2024] [Accepted: 12/15/2024] [Indexed: 12/28/2024]
Abstract
Tryptanthrin and its derivatives, representing a type of alkaloids with indoloquinazoline structures, were first obtained from blue plants and indigo, and then extracted from fungi, marine bacteria and a number of many other natural sources. Various strategies for their chemical synthesis have been reported while tryptanthrin biosynthesis has been less investigated. Tryptanthrin and its derivative products have a broad range of pharmacological and biological functions. In this review, we cover the sources, chemical synthesis and biosynthesis, modes of action and biological activities of tryptanthrin and its derivatives.
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Affiliation(s)
- Khorshed Alam
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China; Bangladesh Standards and Testing Institution (BSTI), Dhaka 1208, Bangladesh.
| | - Md Sawkat Hossain
- Chittagong Medical College Hospital, K B Fazlul Kader Road, Panchlaish, Chattogram 4203, Bangladesh.
| | - Yiming Zhao
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China.
| | - Zhiheng Zhang
- Haide College, Ocean University of China, Qingdao 266100, China.
| | - Shouying Xu
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China.
| | - Jinfang Hao
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China.
| | - Qing Yang
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Songhu Road 2005, Shanghai 200438, China.
| | - Aiying Li
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China.
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3
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Fiorucci S, Urbani G, Biagioli M, Sepe V, Distrutti E, Zampella A. Bile acids and bile acid activated receptors in the treatment of Covid-19. Biochem Pharmacol 2024; 228:115983. [PMID: 38081371 DOI: 10.1016/j.bcp.2023.115983] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 12/06/2023] [Accepted: 12/08/2023] [Indexed: 09/20/2024]
Abstract
Since its first outbreak in 2020, the pandemic caused by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) has caused the death of almost 7 million people worldwide. Vaccines have been fundamental in disease prevention and to reduce disease severity especially in patients with comorbidities. Nevertheless, treatment of COVID-19 has been proven difficult and several approaches have failed to prevent disease onset or disease progression, particularly in patients with comorbidities. Interrogation of drug data bases has been widely used since the beginning of pandemic to repurpose existing drugs/natural substances for the prevention/treatment of COVID-19. Steroids, including bile acids such as ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) have shown to be promising for their potential in modulating SARS-CoV-2/host interaction. Bile acids have proven to be effective in preventing binding of spike protein with the Angiotensin Converting Enzyme II (ACE2), thus preventing virus uptake by the host cells and inhibiting its replication, as well as in indirectly modulating immune response. Additionally, the two main bile acid activated receptors, GPBAR1 and FXR, have proven effective in modulating the expression of ACE2, suggesting an indirect role for these receptors in regulating SARS-CoV-2 infectiveness and immune response. In this review we have examined how the potential of bile acids and their receptors as anti-COVID-19 therapies and how these biochemical mechanisms translate into clinical efficacy.
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Affiliation(s)
- Stefano Fiorucci
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
| | - Ginevra Urbani
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Michele Biagioli
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Valentina Sepe
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | | | - Angela Zampella
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
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Chen J, Zhao Y, Cheng J, Wang H, Pan S, Liu Y. The Antiviral Potential of Perilla frutescens: Advances and Perspectives. Molecules 2024; 29:3328. [PMID: 39064906 PMCID: PMC11279397 DOI: 10.3390/molecules29143328] [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: 06/07/2024] [Revised: 07/11/2024] [Accepted: 07/12/2024] [Indexed: 07/28/2024] Open
Abstract
Viruses pose a significant threat to human health, causing widespread diseases and impacting the global economy. Perilla frutescens, a traditional medicine and food homologous plant, is well known for its antiviral properties. This systematic review examines the antiviral potential of Perilla frutescens, including its antiviral activity, chemical structure and pharmacological parameters. Utilizing bioinformatics analysis, we revealed the correlation between Perilla frutescens and antiviral activity, identified overlaps between Perilla frutescens target genes and virus-related genes, and explored related signaling pathways. Moreover, a classified summary of the active components of Perilla frutescens, focusing on compounds associated with antiviral activity, provides important clues for optimizing the antiviral drug development of Perilla frutescens. Our findings indicate that Perilla frutescens showed a strong antiviral effect, and its active ingredients can effectively inhibit the replication and spread of a variety of viruses in this review. The antiviral mechanisms of Perilla frutescens may involve several pathways, including enhanced immune function, modulation of inflammatory responses, and inhibition of key enzyme activities such as viral replicase. These results underscore the potential antiviral application of Perilla frutescens as a natural plant and provide important implications for the development of new antiviral drugs.
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Affiliation(s)
- Jing Chen
- Department of Bioinformatics and Intelligent Diagnosis, School of Medicine, Jiangsu University, Zhenjiang 212003, China; (J.C.); (Y.Z.); (J.C.); (H.W.)
| | - Yi Zhao
- Department of Bioinformatics and Intelligent Diagnosis, School of Medicine, Jiangsu University, Zhenjiang 212003, China; (J.C.); (Y.Z.); (J.C.); (H.W.)
| | - Jie Cheng
- Department of Bioinformatics and Intelligent Diagnosis, School of Medicine, Jiangsu University, Zhenjiang 212003, China; (J.C.); (Y.Z.); (J.C.); (H.W.)
| | - Haoran Wang
- Department of Bioinformatics and Intelligent Diagnosis, School of Medicine, Jiangsu University, Zhenjiang 212003, China; (J.C.); (Y.Z.); (J.C.); (H.W.)
| | - Shu Pan
- Computer Science School, Jiangsu University of Science and Technology, Zhenjiang 212003, China;
| | - Yuwei Liu
- Department of Bioinformatics and Intelligent Diagnosis, School of Medicine, Jiangsu University, Zhenjiang 212003, China; (J.C.); (Y.Z.); (J.C.); (H.W.)
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Mustafa Din W, Arham AF, Md. Yusoff Y. Set of data on consumers' perceived safety and efficacy towards natural health products to control or cure Covid-19 viruses in Malaysia. Data Brief 2024; 54:110548. [PMID: 38912420 PMCID: PMC11190492 DOI: 10.1016/j.dib.2024.110548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Revised: 05/17/2024] [Accepted: 05/17/2024] [Indexed: 06/25/2024] Open
Abstract
This study evaluated the level of knowledge of effects, knowledge of safe use, information complexity of natural health products and consumers' perceived safety and efficacy toward natural health products used to control or cure Covid-19 viruses in Malaysia. The validated questionnaires were used to survey randomly selected stakeholders in Malaysia, who were asked to participate voluntarily in an online survey from 1st September 2020 to 31st December 2020. 723 respondents of adults above 18 years old returned completed questionnaires. The survey used for data collection consisted of 5 questions on knowledge of effects, 4 questions on knowledge for safe-use, 9 questions on perception towards safety and efficacy and 4 questions on the information complexity of natural health products. Besides that, 8 questions are being asked on the demography of respondents at the very end of the survey. The Statistical Package for the Social Sciences (SPSS) version 26 was used to analyse the data. The mean score, correlation and regression values were the focus of this study. The findings provide various opportunities to investigate Malaysian consumers' perceptions which facilitates the development of regulation and strategic plans related to health, and encourage additional research by other researchers interested in the measures and data given.
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Affiliation(s)
- Wardah Mustafa Din
- School of Liberal Studies, Universiti Kebangsaan Malaysia, 43650 Bangi, Malaysia
| | - Ahmad Firdhaus Arham
- School of Liberal Studies, Universiti Kebangsaan Malaysia, 43650 Bangi, Malaysia
| | - Yusnaini Md. Yusoff
- School of Liberal Studies, Universiti Kebangsaan Malaysia, 43650 Bangi, Malaysia
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Hassan Kalantar Neyestanaki M, Gholizadeh O, Hosseini Tabatabaie F, Akbarzadeh S, Yasamineh S, Afkhami H, Sedighi S. Immunomodulatory effects of cannabinoids against viral infections: a review of its potential use in SARS-CoV2 infection. Virusdisease 2024; 35:342-356. [PMID: 39071880 PMCID: PMC11269557 DOI: 10.1007/s13337-024-00871-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Accepted: 05/11/2024] [Indexed: 07/30/2024] Open
Abstract
The COVID-19 pandemic is a global health crisis affecting millions of people worldwide. Along with vaccine development, there is also a priority to discover new drugs and treatments. One approach involves modulating the immune system to manage inflammation and cytokine storms. Patients with a high severity of complications exhibit a high level of inflammatory cytokines, particularly IL-6, in the airways and other infected tissues. Several studies have reported the function of the endocannabinoid system in regulating inflammation and different immune responses. Cannabinoids are a class of natural chemicals found in the Cannabis plant. Recently, the anti-inflammatory properties of cannabinoids and their mediatory immunosuppression mechanisms through the endocannabinoid system have engrossed scientists in the health field for infectious conditions. Research suggests that the immune system can regulate cytokine activation through cannabinoid receptors, particularly with Cannabidiol (CBD), the second most prevalent compound in cannabis. While CBD has been deemed safe by the World Health Organization and shows no signs of abuse potential, excessive CBD use may lead to respiratory depression. CBD shows promise in reducing immune cell recruitment and cytokine storms in organs affected by SARS-CoV2. However, before clinical use, it's crucial to evaluate cannabinoid-based medications' active ingredient concentrations and potential interactions with other drugs, along with associated side effects. Indication-based dosing, consistent formulations, and ensuring purity and potency are essential. This review highlights cannabinoids' effects on COVID-19 management and prognosis, drawing from preclinical and clinical studies.
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Affiliation(s)
| | | | - Fatemeh Hosseini Tabatabaie
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sama Akbarzadeh
- Department of Animal Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran
| | - Saman Yasamineh
- Young Researchers and Elite Club, Tabriz Branch, Islamic Azad University, Tabriz, Iran
| | - Hamed Afkhami
- Department of Medical Microbiology, Faculty of Medicine, Shahed University of Medical Science, Tehran, Iran
| | - Somayeh Sedighi
- Department of Immunology, Faculty of Medicine, Medical Science of Mashhad, Mashhad, Iran
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Shahzadi Z, Yousaf Z, Anjum I, Bilal M, Yasin H, Aftab A, Booker A, Ullah R, Bari A. Network pharmacology and molecular docking: combined computational approaches to explore the antihypertensive potential of Fabaceae species. BIORESOUR BIOPROCESS 2024; 11:53. [PMID: 38767701 PMCID: PMC11106056 DOI: 10.1186/s40643-024-00764-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 04/26/2024] [Indexed: 05/22/2024] Open
Abstract
Hypertension is a major global public health issue, affecting quarter of adults worldwide. Numerous synthetic drugs are available for treating hypertension; however, they often come with a higher risk of side effects and long-term therapy. Modern formulations with active phytoconstituents are gaining popularity, addressing some of these issues. This study aims to discover novel antihypertensive compounds in Cassia fistula, Senna alexandrina, and Cassia occidentalis from family Fabaceae and understand their interaction mechanism with hypertension targeted genes, using network pharmacology and molecular docking. Total 414 compounds were identified; initial screening was conducted based on their pharmacokinetic and ADMET properties, with a particular emphasis on adherence to Lipinski's rules. 6 compounds, namely Germichrysone, Benzeneacetic acid, Flavan-3-ol, 5,7,3',4'-Tetrahydroxy-6, 8-dimethoxyflavon, Dihydrokaempferol, and Epiafzelechin, were identified as effective agents. Most of the compounds found non-toxic against various indicators with greater bioactivity score. 161 common targets were obtained against these compounds and hypertension followed by compound-target network construction and protein-protein interaction, which showed their role in diverse biological system. Top hub genes identified were TLR4, MMP9, MAPK14, AKT1, VEGFA and HSP90AA1 with their respective associates. Higher binding affinities was found with three compounds Dihydrokaempferol, Flavan-3-ol and Germichrysone, -7.1, -9.0 and -8.0 kcal/mol, respectively. The MD simulation results validate the structural flexibility of two complexes Flavan-MMP9 and Germich-TLR4 based on no. of hydrogen bonds, root mean square deviations and interaction energies. This study concluded that C. fistula (Dihydrokaempferol, Flavan-3-ol) and C. occidentalis (Germichrysone) have potential therapeutic active constituents to treat hypertension and in future novel drug formulation.
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Affiliation(s)
- Zainab Shahzadi
- Department of Botany, Lahore College for Women University, Lahore, Pakistan
| | - Zubaida Yousaf
- Department of Botany, Lahore College for Women University, Lahore, Pakistan.
| | - Irfan Anjum
- Department of Basic Medical Sciences, Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, Islamabad, Pakistan
| | - Muhammad Bilal
- Centers for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Hamna Yasin
- Department of Botany, Lahore College for Women University, Lahore, Pakistan
| | - Arusa Aftab
- Department of Botany, Lahore College for Women University, Lahore, Pakistan
| | - Anthony Booker
- Research Centre for Optimal Health, School of Life Sciences, College of Liberal Arts and Sciences, University of Westminster, 115 New Cavendish Street, London, W1W 6UW, UK.
- Research Group 'Pharmacognosy and Phytotherapy', UCL School of Pharmacy, Univ. London, 29 - 39 Brunswick Sq., London, WC1N 1AX, UK.
| | - Riaz Ullah
- Department of Pharmacognosy, College of Pharmacy King, Saud University, Riyadh, Saudi Arabia
| | - Ahmed Bari
- Department of Pharmaceutical Chemistry, College of Pharmacy King, Saud University, Riyadh, Saudi Arabia
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8
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Huang FP, Qin WJ, Pan XY, Yang K, Wang K, Teng QH. Visible-Light-Induced Chemodivergent Synthesis of Tetracyclic Quinazolinones and 3-Iminoisoindoliones via the Substrate Control Strategy. J Org Chem 2024; 89:4395-4405. [PMID: 38501298 DOI: 10.1021/acs.joc.3c02501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/20/2024]
Abstract
A visible-light-induced chemodivergent synthesis of tetracyclic quinazolinones and 3-iminoisoindoliones has been developed. This chemodivergent reaction afforded two kinds of different products by substrate control. A detailed investigation of the reaction mechanism revealed that this consecutive photoinduced electron transfer (ConPET) cascade cyclization involved a radical process, and the aryl radical was the crucial intermediate. This method employed 4-DPAIPN as a photocatalyst and i-Pr2NEt as a sacrificial electron donor leading to metal-free conditions.
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Affiliation(s)
- Fang-Ping Huang
- Guangxi Key Laboratory of Electrochemical and Magnetochemical Functional Materials, College of Chemistry and Bioengineering, Guilin University of Technology, Guilin 541004, China
| | - Wen-Jian Qin
- Guangxi Key Laboratory of Electrochemical and Magnetochemical Functional Materials, College of Chemistry and Bioengineering, Guilin University of Technology, Guilin 541004, China
| | - Xin-Yao Pan
- Guangxi Key Laboratory of Electrochemical and Magnetochemical Functional Materials, College of Chemistry and Bioengineering, Guilin University of Technology, Guilin 541004, China
| | - Kun Yang
- Guangxi Key Laboratory of Electrochemical and Magnetochemical Functional Materials, College of Chemistry and Bioengineering, Guilin University of Technology, Guilin 541004, China
| | - Kai Wang
- Guangxi Key Laboratory of Electrochemical and Magnetochemical Functional Materials, College of Chemistry and Bioengineering, Guilin University of Technology, Guilin 541004, China
| | - Qing-Hu Teng
- Guangxi Key Laboratory of Electrochemical and Magnetochemical Functional Materials, College of Chemistry and Bioengineering, Guilin University of Technology, Guilin 541004, China
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Gao S, Cai M, Xu G, Jin Q, Wang X, Xu L, Wang L, Dai L. (NH 4) 2S 2O 8 promoted tandem radical cyclization of quinazolin-4(3 H)-ones with oxamic acids for the construction of fused quinazolinones under metal-free conditions. Org Biomol Chem 2024; 22:2241-2251. [PMID: 38372133 DOI: 10.1039/d3ob02081a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/20/2024]
Abstract
A novel cascade radical addition/cyclization reaction of non-activated olefins and oxamic acids has been proposed. Under transition metal-free conditions, 36 quinazolinone derivatives containing an amide moiety were successfully synthesized, with the highest yield being 81%. This method involves the preparation of aminoacyl fused quinazolinone derivatives under mild conditions, offering advantages such as a high yield, a broad substrate compatibility, and a high atom economy.
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Affiliation(s)
- Shenyuan Gao
- Zhejiang Provincial Key Laboratory of Advanced Chemical Engineering Manufacture Technology, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, PR China.
| | - Menglu Cai
- Zhejiang Provincial Key Laboratory of Advanced Chemical Engineering Manufacture Technology, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, PR China.
- Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 310027, PR China.
| | - Gang Xu
- Zhejiang Provincial Key Laboratory of Advanced Chemical Engineering Manufacture Technology, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, PR China.
| | - Qiaolin Jin
- Zhejiang Provincial Key Laboratory of Advanced Chemical Engineering Manufacture Technology, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, PR China.
| | - Xiaozhong Wang
- Zhejiang Provincial Key Laboratory of Advanced Chemical Engineering Manufacture Technology, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, PR China.
| | - Linze Xu
- Zhejiang Provincial Key Laboratory of Advanced Chemical Engineering Manufacture Technology, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, PR China.
| | - Lixiang Wang
- Zhejiang Provincial Key Laboratory of Advanced Chemical Engineering Manufacture Technology, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, PR China.
| | - Liyan Dai
- Zhejiang Provincial Key Laboratory of Advanced Chemical Engineering Manufacture Technology, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, PR China.
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10
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Tang JJ, Zhao MY, Lin YJ, Yang LH, Xie LY. Persulfate-Promoted Carbamoylation/Cyclization of Alkenes: Synthesis of Amide-Containing Quinazolinones. Molecules 2024; 29:997. [PMID: 38474508 DOI: 10.3390/molecules29050997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 02/22/2024] [Accepted: 02/24/2024] [Indexed: 03/14/2024] Open
Abstract
The incorporation of amide groups into biologically active molecules has been proven to be an efficient strategy for drug design and discovery. In this study, we present a simple and practical method for the synthesis of amide-containing quinazolin-4(3H)-ones under transition-metal-free conditions. This is achieved through a carbamoyl-radical-triggered cascade cyclization of N3-alkenyl-tethered quinazolinones. Notably, the carbamoyl radical is generated in situ from the oxidative decarboxylative process of oxamic acids in the presence of (NH4)2S2O8.
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Affiliation(s)
- Jia-Jun Tang
- College of Chemistry and Bioengineering, Hunan University of Science and Engineering, Yongzhou 425100, China
| | - Meng-Yang Zhao
- College of Chemistry and Bioengineering, Hunan University of Science and Engineering, Yongzhou 425100, China
| | - Ying-Jun Lin
- College of Chemistry and Bioengineering, Hunan University of Science and Engineering, Yongzhou 425100, China
| | - Li-Hua Yang
- College of Chemistry and Bioengineering, Hunan University of Science and Engineering, Yongzhou 425100, China
| | - Long-Yong Xie
- College of Chemistry and Bioengineering, Hunan University of Science and Engineering, Yongzhou 425100, China
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Khazir J, Ahmed S, Thakur RK, Hussain M, Gandhi SG, Babbar S, Mir SA, Shafi N, Tonfack LB, Rajpal VR, Maqbool T, Mir BA, Peer LA. Repurposing of Plant-based Antiviral Molecules for the Treatment of COVID-19. Curr Top Med Chem 2024; 24:614-633. [PMID: 38477206 DOI: 10.2174/0115680266276749240206101847] [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: 09/28/2023] [Revised: 12/30/2023] [Accepted: 01/10/2024] [Indexed: 03/14/2024]
Abstract
COVID-19, stemming from SARS-CoV-2, poses a formidable threat to global healthcare, with a staggering 77 million confirmed cases and 690,067 deaths recorded till December 24, 2023. Given the absence of specific drugs for this viral infection, the exploration of novel antiviral compounds becomes imperative. High-throughput technologies are actively engaged in drug discovery, and there is a parallel effort to repurpose plant-based molecules with established antiviral properties. In this context, the review meticulously delves into the potential of plant-based folk remedies and existing molecules. These substances have showcased substantial viral inhibition in diverse in vivo, in silico, and in vitro studies, particularly against critical viral protein targets, including SARS-CoV-2. The findings position these plant-based molecules as promising antiviral drug candidates for the swift advancement of treatments for COVID-19. It is noteworthy that the inherent attributes of these plant-based molecules, such as their natural origin, potency, safety, and cost-effectiveness, contribute to their appeal as lead candidates. The review advocates for further exploration through comprehensive in vivo studies conducted on animal models, emphasizing the potential of plant-based compounds to help in the ongoing quest to develop effective antivirals against COVID-19.
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Affiliation(s)
- Jabeena Khazir
- Department of Chemistry, HKM Govt. Degree College Eidgah, Cluster University Srinagar, J&K, 190001, India
| | - Sajad Ahmed
- Indian Institute of Integrative Medicine, Canal Road Jammu, 180001, J&K, India
| | - Rakesh Kr Thakur
- Amity Institute of Biotechnology, Amity University, Noida, 201313, India
| | - Manzoor Hussain
- Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, 143005, Punjab, India
- Department of Botany, North Campus, University of Kashmir, Delina, Baramulla, J&K, 193103, India
| | - Sumit G Gandhi
- Indian Institute of Integrative Medicine, Canal Road Jammu, 180001, J&K, India
| | - Sadhana Babbar
- Department of Botany, Swami Shradhanand College, University of Delhi, Delhi, 110036, India
| | - Shabir Ahmad Mir
- Department of Medical Laboratory Sciences, College of Applied Medical Science, Majmaah University, Al Majmaah, 11952, Saudi Arabia
| | - Nusrat Shafi
- Department of Chemistry, HKM Govt. Degree College Eidgah, Cluster University Srinagar, J&K, 190001, India
| | - Libert Brice Tonfack
- Laboratory of Biotechnology and Environment, Department of Plant Biology, Faculty of Science, University of Yaounde I, PO Box 812, Yaounde, Cameroon
| | - Vijay Rani Rajpal
- Department of Botany, Hans Raj College, University of Delhi, Delhi, 110007, India
| | - Tariq Maqbool
- Laboratory of Nanotherapeutics and Regenerative Medicine, University of Kashmir, Srinagar, 190006, India
| | - Bilal Ahmad Mir
- Department of Botany, North Campus, University of Kashmir, Delina, Baramulla, J&K, 193103, India
| | - Latif Ahmad Peer
- Department of Botany, University of Kashmir, Srinagar, J&K, 190006, India
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12
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Ameri A, Farashahinejad M, Davoodian P, Safa O, Kusha A, Dadvand H, Hassanipour S, Fathalipour M. Efficacy and safety of licorice (Glycyrrhiza glabra) in moderately ill patients with COVID-19: a randomized controlled trial. Inflammopharmacology 2023; 31:3037-3045. [PMID: 37847472 DOI: 10.1007/s10787-023-01352-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 09/21/2023] [Indexed: 10/18/2023]
Abstract
Licorice extract (glycyrrhizin), a potent antiviral, anti-inflammatory, and antioxidant remedy, is a potential therapeutic option for COVID-19. We evaluated the efficacy and safety of licorice in patients with moderate COVID-19. In this study, 60 patients with confirmed COVID-19 were randomly assigned in a 1:1 ratio to receive licorice (at a dose of 760 mg three times a day for seven days) or control groups. The primary outcomes were SPO2, body temperature, and respiratory rate (RR) after the end of the intervention. The findings indicated that SPO2, body temperature, and RR had no significant difference between the groups at the end of the intervention. However, CRP and ALT improved in the licorice group toward the baseline. The number of patients with worse prognoses, LOS, mortality, and the incidence of adverse events were not different between the groups at the end of the study. Licorice had no beneficial effect on the clinical symptoms of COVID-19. Moreover, this intervention demonstrated a safe profile of adverse events. The confirmation of the results of this preparatory trial requires more detailed multiple-center trials with a larger sample size.
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Affiliation(s)
- Ali Ameri
- Student Research Committee, Faculty of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Mehdi Farashahinejad
- Infectious and Tropical Diseases Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Parivash Davoodian
- Infectious and Tropical Diseases Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Omid Safa
- Department of Clinical Pharmacy, Faculty of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Amin Kusha
- Infectious and Tropical Diseases Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Habib Dadvand
- Infectious and Tropical Diseases Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Soheil Hassanipour
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Mohammad Fathalipour
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
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13
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He Z, Yuan J, Zhang Y, Li R, Mo M, Wang Y, Ti H. Recent advances towards natural plants as potential inhibitors of SARS-Cov-2 targets. PHARMACEUTICAL BIOLOGY 2023; 61:1186-1210. [PMID: 37605622 PMCID: PMC10446791 DOI: 10.1080/13880209.2023.2241518] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 05/29/2023] [Accepted: 07/23/2023] [Indexed: 08/23/2023]
Abstract
CONTEXT Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still ongoing and currently the most striking epidemic disease. With the rapid global spread of SARS-CoV-2 variants, new antivirals are urgently needed to avert a more serious crisis. Inhibitors from traditional medicines or natural plants have shown promising results to fight COVID-19 with different mechanisms of action. OBJECTIVES To provide comprehensive and promising approaches to the medical community in the fight against this epidemic by reviewing potential plant-derived anti-SARS-CoV-2 inhibitors. METHODS Structural databases such as TCMSP (http://lsp.nwu.edu.cn/tcmsp.php), TCM Database @ Taiwan (http://tcm.cmu.edu.tw/), BATMAN-TCM (http://bionet.ncpsb.org/batman-tcm/) and TCMID (http://www.megabionet.org/tcmid/), as well as PubMed, Sci Finder, Research Gate, Science Direct, CNKI, Web of Science and Google Scholar were searched for relevant articles on TCMs and natural products against SARS-CoV-2. RESULTS Seven traditional Chinese medicines formulas have unique advantages in regulating the immune system for treating COVID-19. The plant-derived natural compounds as anti-SARS-CoV-2 inhibitors were identified based on 5 SARS-CoV-2 key proteins, namely, angiotensin-converting enzyme 2 (ACE2), 3 C-like protease (3CLpro), papain-like protease (PLpro), spike (S) protein, and nucleocapsid (N) protein. CONCLUSIONS A variety of natural products, such as flavonoids, terpenoids, phenols, and alkaloids, were identified, which could be used as potential SASR-Cov-2 inhibitors. These shed new light on the efficient discovery of SASR-Cov-2 inhibitors from natural products.
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Affiliation(s)
- Zhouman He
- School of Chinese Medicinal Resource, Guangdong Pharmaceutical University, Guangzhou, P. R. China
| | - Jia Yuan
- School of Chinese Medicinal Resource, Guangdong Pharmaceutical University, Guangzhou, P. R. China
| | - Yuanwen Zhang
- School of Chinese Medicinal Resource, Guangdong Pharmaceutical University, Guangzhou, P. R. China
| | - Runfeng Li
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, P. R. China
| | - Meilan Mo
- School of Chinese Medicinal Resource, Guangdong Pharmaceutical University, Guangzhou, P. R. China
| | - Yutao Wang
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, P. R. China
| | - Huihui Ti
- School of Chinese Medicinal Resource, Guangdong Pharmaceutical University, Guangzhou, P. R. China
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14
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Ma R, Song N, Wang L, Gu X, Xiong F, Zhang S, Zhang J, Yang W, Zuo Z. Discovery of 2-(Methylcarbonylamino) thiazole as PDE4 inhibitors via virtual screening and biological evaluation. J Mol Graph Model 2023; 124:108567. [PMID: 37481883 DOI: 10.1016/j.jmgm.2023.108567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 06/30/2023] [Accepted: 07/12/2023] [Indexed: 07/25/2023]
Abstract
Phosphodiesterase-4, the primary enzyme responsible for cAMP degradation in the majority of immune and inflammatory cells, plays a critical role in the regulation of intracellular cAMP levels. Consequently, small molecular entities capable of inhibiting PDE4 have been employed in the treatment of inflammation-associated disorders, such as chronic obstructive pulmonary disease (COPD), psoriasis, atopic dermatitis (AD), inflammatory bowel diseases (IBD), rheumatic arthritis (RA). In the present investigation, a multi-faceted approach was employed to identify novel PDE4 inhibitors, utilizing the co-crystallization structure of PDE4B available in the Protein Data Bank (PDB) database, drug-like screening, false positive filtration, similarity and ADMET screen, as well as molecular docking via multiple software platforms, in conjunction with bioactivity assays. A thiazol-3-propanamides derivative, designated MR9, was discovered to inhibit PDE4B activity with IC50 values of 2.12 μM and suppress cellular inflammatory factor TNF-α release with an EC50 value of 3.587 μM. These findings suggest that the innovative active scaffold of MR9 offers a promising foundation for further structural refinement aimed at developing more potent PDE4 inhibitors.
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Affiliation(s)
- Rui Ma
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China
| | - Na Song
- School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, 650500, PR China
| | - Lveli Wang
- School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, 650500, PR China
| | - Xi Gu
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, PR China
| | - Feng Xiong
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, PR China
| | - Shuqun Zhang
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, PR China
| | - Jie Zhang
- School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, 650500, PR China
| | - Weimin Yang
- School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, 650500, PR China.
| | - Zhili Zuo
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China.
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15
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Couto JCM, Vidal T, Decker ER, Santurio JM, Mello CF, Pillat MM. Use of recombinant S1 protein with hFc for analysis of SARS-CoV-2 adsorption and evaluation of drugs that inhibit entry into VERO E6 cells. Immunol Lett 2023; 263:105-112. [PMID: 37683695 DOI: 10.1016/j.imlet.2023.09.002] [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: 11/30/2022] [Revised: 06/07/2023] [Accepted: 09/05/2023] [Indexed: 09/10/2023]
Abstract
The significant number of deaths and infection caused by the new coronavirus SARS-CoV-2 has created an urgent demand for effective and readily available drugs for the treatment of COVID-19. However, the requirements for biosafety level 3 (NB-3) laboratories for experiments with the virus has made it very challenging for such research to meet this demand. It is known that angiotensin-converting enzyme 2 (ACE2), located on the surface of host cells, serves as the viral receptor for the spike (S) protein of SARS-CoV-2. This protein is a tetramer subdivided into S1 and S2 regions, with the former containing the receptor-binding domain (RBD). Therefore, drugs that interfere with the interaction between the spike and the receptor (as well as accessory proteins) or suppress their expression could inhibit the entry and spread of SARS-CoV-2 between cells. In this context, we standardized the use of recombinant SARS-CoV-2 S1 Protein with hFc (human Fc) for the analysis of binding in VERO E6 cells by flow cytometry, aiming to provide a new tool for identifying drugs and neutralizing antibodies, thus eliminating the need for NB-3 laboratories. Because minocycline (MCL), nimesulide (NMS), and berberine (BBR) have effects related to the ACE2 receptor, inhibit inflammation, and do not suppress the adaptive immune response (crucial for patient recovery), we investigated whether these drugs prevent the absorption of the spike protein into the host cell. For this purpose, we used VERO E6 cells under control conditions, pre-treated with these drugs and exposed to recombinant SARS-CoV-2 S1 Protein with hFC. We found that an exposure time of 30 min and a concentration of 10 μg/mL of spike S1 caused a strong signal detected by flow cytometry, using the secondary anti-hFc antibody conjugated with Alexa Fluor 647. Pre-treatment of cells with BBR for 30 min suppressed the signal from spike-positive cells, suggesting that this alkaloid interferes with spike adsorption on ACE2. The pre-incubation of spike protein with BBR did not alter its adsorption and internalization, indicating that BBR does not directly interact with spike protein. The ACE2 inactivation with a specific antibody inhibited spike protein adsorption and internalization. Furthermore, the pharmacological treatments did not alter the expression of ACE2. Exposure to spike protein increased IFNγ levels and the treatments with MCL and NMS were effective in inhibiting this increase. Taken together, we standardized a technique for analyzing the adsorption of SARS-CoV-2 and studying molecules that inhibit this process. Additionally, we demonstrated that BBR blocks spike entry bypre-binding to the host cell,and that the ACE2 receptor inactivation prevents Spike protein adsorption and penetration into cells.
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Affiliation(s)
- Jéssica Carla Martins Couto
- Programa de Pós-graduação em Farmacologia. Universidade Federal de Santa Maria, Building 15B, Roraima Av. 1000, Santa Maria, RS 97105900, Brazil.
| | - Taís Vidal
- Programa de Pós-graduação em Ciências Farmacêuticas. Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
| | | | - Janio M Santurio
- Programa de Pós-graduação em Ciências Farmacêuticas. Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
| | - Carlos Fernando Mello
- Programa de Pós-graduação em Farmacologia. Universidade Federal de Santa Maria, Building 15B, Roraima Av. 1000, Santa Maria, RS 97105900, Brazil
| | - Micheli Mainardi Pillat
- Programa de Pós-graduação em Farmacologia. Universidade Federal de Santa Maria, Building 15B, Roraima Av. 1000, Santa Maria, RS 97105900, Brazil; Programa de Pós-graduação em Ciências Farmacêuticas. Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
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16
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Zaa CA, Espitia C, Reyes-Barrera KL, An Z, Velasco-Velázquez MA. Neuroprotective Agents with Therapeutic Potential for COVID-19. Biomolecules 2023; 13:1585. [PMID: 38002267 PMCID: PMC10669388 DOI: 10.3390/biom13111585] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 10/19/2023] [Accepted: 10/20/2023] [Indexed: 11/26/2023] Open
Abstract
COVID-19 patients can exhibit a wide range of clinical manifestations affecting various organs and systems. Neurological symptoms have been reported in COVID-19 patients, both during the acute phase of the illness and in cases of long-term COVID. Moderate symptoms include ageusia, anosmia, altered mental status, and cognitive impairment, and in more severe cases can manifest as ischemic cerebrovascular disease and encephalitis. In this narrative review, we delve into the reported neurological symptoms associated with COVID-19, as well as the underlying mechanisms contributing to them. These mechanisms include direct damage to neurons, inflammation, oxidative stress, and protein misfolding. We further investigate the potential of small molecules from natural products to offer neuroprotection in models of neurodegenerative diseases. Through our analysis, we discovered that flavonoids, alkaloids, terpenoids, and other natural compounds exhibit neuroprotective effects by modulating signaling pathways known to be impacted by COVID-19. Some of these compounds also directly target SARS-CoV-2 viral replication. Therefore, molecules of natural origin show promise as potential agents to prevent or mitigate nervous system damage in COVID-19 patients. Further research and the evaluation of different stages of the disease are warranted to explore their potential benefits.
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Affiliation(s)
- César A. Zaa
- School of Biological Sciences, Universidad Nacional Mayor de San Marcos (UNMSM), Lima 15081, Peru;
| | - Clara Espitia
- Department of Immunology, Institute of Biomedical Research, Universidad Nacional Autónoma de México (UNAM), Mexico City 04510, Mexico; (C.E.); (K.L.R.-B.)
| | - Karen L. Reyes-Barrera
- Department of Immunology, Institute of Biomedical Research, Universidad Nacional Autónoma de México (UNAM), Mexico City 04510, Mexico; (C.E.); (K.L.R.-B.)
| | - Zhiqiang An
- Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USA;
| | - Marco A. Velasco-Velázquez
- Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USA;
- School of Medicine, Universidad Nacional Autónoma de México (UNAM), Mexico City 04510, Mexico
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17
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Elkousy RH, Said ZNA, Ali MA, Kutkat O, Abu El Wafa SA. Anti-SARS-CoV-2 in vitro potential of castor oil plant ( Ricinus communis) leaf extract: in-silico virtual evidence. Z NATURFORSCH C 2023; 78:365-376. [PMID: 37401758 DOI: 10.1515/znc-2023-0075] [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: 04/27/2023] [Accepted: 06/21/2023] [Indexed: 07/05/2023]
Abstract
Ricinus communis L. is a medicinal plant that displays valuable pharmacological properties, including antioxidant, antimicrobial, analgesic, antibacterial, antiviral and anti-inflammatory properties. This study targeted to isolate and identify some constituents of R. communis leaves using ultra-performance liquid chromatography coupled with mass spectroscopy (UPLC-MS/MS) and different chromatographic techniques. In vitro anti-MERS and anti-SARS-CoV-2 activity for different fractions and for two pure isolated compounds, lupeol (RS) and ricinine (RS1) were evaluated using a plaque reduction assay with three different mechanisms and IC50 based on their cytotoxic concentration (CC50) from an MTT assay using Vero E6 cell line. Isolated phytoconstituents and remdesivir are assessed for in-silico anti-COVID-19 activity using molecular docking tools. The methylene chloride extract showed pronounced virucidal activity against SARS-CoV-2 (IC50 = 1.76 μg/ml). It was also shown that ricinine had superior potential activity against SARS-CoV-2, (IC50 = 2.5 μg/ml). Lupeol displayed the most potency against MERS, (IC50 = 5.28 μg/ml). Ricinine appeared to be the most biologically active compound. The study showed that R. communis and its isolated compounds have potential natural virucidal activity against SARS-COV-2; however, additional exploration is necessary and study for their in vivo activity.
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Affiliation(s)
- Rawah H Elkousy
- Department of Pharmacognosy and Medicinal Plants, Faculty of Pharmacy (for Girls), Al-Azhar University, P.O. Box 11651, Nasr City, Cairo, Egypt
| | - Zeinab N A Said
- Department of Medical Microbiology & Immunology, Faculty of Medicine (for Girls), Al-Azhar University, P.O. Box 11754, Nasr City, Cairo, Egypt
| | - Mohamed A Ali
- Center of Scientific Excellence for Influenza Viruses, National Research Centre, P.O. Box 12622, Giza, Egypt
| | - Omnia Kutkat
- Center of Scientific Excellence for Influenza Viruses, National Research Centre, P.O. Box 12622, Giza, Egypt
| | - Salwa A Abu El Wafa
- Department of Pharmacognosy and Medicinal Plants, Faculty of Pharmacy (for Girls), Al-Azhar University, P.O. Box 11651, Nasr City, Cairo, Egypt
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18
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Li J, Wang Y, Rajpoot S, Lavrijsen M, Pan Q, Li P, Baig MS. Investigating theobromine as a potential anti-human coronaviral agent. Microbiol Immunol 2023; 67:404-412. [PMID: 37415325 DOI: 10.1111/1348-0421.13086] [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: 12/22/2022] [Revised: 05/08/2023] [Accepted: 06/08/2023] [Indexed: 07/08/2023]
Abstract
Coronaviruses (CoVs) have long been known to infect humans, mainly alpha-CoV and beta-CoV. The vaccines developed for SARS-CoV-2 are likely not effective against other coronavirus species, whereas the risk of the emergence of new strains that may cause the next epidemic/pandemic is high. The development of antiviral drugs that are effective across different CoVs represents a viable strategy for improving pandemic preparedness. In this study, we aim to identify pan-coronaviral agents by targeting the conserved main protease (Mpro). For drug screening, the catalytic dyad of four human CoVs (HCoVs: SARS-CoV-2, and seasonal CoV NL63, OC43, and 229E) was targeted by molecular docking. The identified leading candidate theobromine, a xanthine derivative, was further tested in cell culture models of coronavirus infection. Theobromine binds strongly with the catalytic dyad (His41 and Cys144/145) of SARS-CoV-2 and HCoV-NL63 Mpro, mildly with HCoV-OC43, but not with HCoV-229E. However, theobromine only shows dose-dependent inhibition in Calu3 cells inoculated with SARS-CoV-2, but not in cells inoculated with seasonal CoVs. Theobromine exerts antiviral activity against coronavirus infections potentially through targeting Mpro. However, the antiviral potency is distinct among different CoVs.
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Affiliation(s)
- Jiajing Li
- Department of Gastroenterology & Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Yining Wang
- Department of Gastroenterology & Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Sajjan Rajpoot
- Department of Biosciences & Biomedical Engineering (BSBE), Indian Institute of Technology Indore (IITI), Indore, India
| | - Marla Lavrijsen
- Department of Gastroenterology & Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Qiuwei Pan
- Department of Gastroenterology & Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Pengfei Li
- Department of Gastroenterology & Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Mirza S Baig
- Department of Biosciences & Biomedical Engineering (BSBE), Indian Institute of Technology Indore (IITI), Indore, India
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19
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Raman K, Rajagopal K, Swaminathan G, Jupudi S, Dhama K, Barua R, Emran TB, Osman H, Khandaker MU. A Critical Review on the Potency of Phytoconstituents in the Management of COVID-19. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2023; 17:1320-1340. [DOI: 10.22207/jpam.17.3.38] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/12/2024] Open
Abstract
Natural products and their derivatives have traditionally been used as a source of therapeutic agents. Their beneficial properties are due to large varieties in their chemical structures and biochemical actions. The discovery of natural products such as phytoconstituents have crucial role in the development of less toxic and more effective drugs. Phytoconstituents have shown to be beneficial in treating viral diseases such as the previous chikungunya virus, hepatitis C virus, SARS, and MERS viral diseases. Flavonoids, alkaloids, terpenoids, and other group of compounds combat against COVID-19 in several ways like by protease inhibition, spike protein inhibition, Nrf2 inhibition. The accumulation of NRF2 inhibits the development of the SARS-CoV-2 virus and stimulates anti-inflammatory action. The present review highlights the therapeutic importance of compounds isolated from medicinal plants and/or herbs, such as crude extracts of Curcumin I-III, Leptodactylone, Ginsenoside-Rb1, Lycorine, Reserpine, Saikosaponin B2, Cepharanthine, Withanoside V, Gingerol, Piperanine, chromans, flavonoids, Amentoflavone etc. against SARS-CoV-2. Natural products are typically safe, stable, and dependable source for finding drugs to control the current pandemic. Antiviral secondary metabolites many medicinal plants have given ingredients that were isolated. The selected plants based phytoconstituents may potentially be used against viruses’ development on anti-SARS-CoV-2 to offer a reference point in this field.
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20
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Wu HL, Zhang WK, Zhang CC, Wang LT, Yang WH, Tian WC, Ge GP, Xie LY, Yi R, Wei WT. Chemodivergent Tandem Radical Cyclization of Alkene-Substituted Quinazolinones: Rapid Access to Mono- and Di-Alkylated Ring-Fused Quinazolinones. Chemistry 2023; 29:e202301390. [PMID: 37280159 DOI: 10.1002/chem.202301390] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 06/05/2023] [Accepted: 06/06/2023] [Indexed: 06/08/2023]
Abstract
Chemodivergent tandem radical cyclization offers exciting possibilities for the synthesis of structurally diverse cyclic compounds. Herein, we revealed a chemodivergent tandem cyclization of alkene-substituted quinazolinones under metal- and base-free conditions, this transformation is initiated by alkyl radicals produced from oxidant-induced α-C(sp3 )-H functionalization of alkyl nitriles or esters. The reaction resulted in the selective synthesis of a series of mono- and di-alkylated ring-fused quinazolinones by modulating the loading of oxidant, reaction temperature, and reaction time. Mechanistic investigations show that the mono-alkylated ring-fused quinazolinones is constructed by the key process of 1,2-hydrogen shift, whereas the di-alkylated ring-fused quinazolinones is mainly achieved through crucial steps of resonance and proton transfer. This protocol is the first example of remote second alkylation on the aromatic ring via α-C(sp3 )-H functionalization and difunctionalization achieved by association of two unsaturated bonds in radical cyclization.
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Affiliation(s)
- Hong-Li Wu
- School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, Zhejiang, 315211, China
| | - Wei-Kang Zhang
- School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, Zhejiang, 315211, China
| | - Can-Can Zhang
- School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, Zhejiang, 315211, China
| | - Ling-Tao Wang
- School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, Zhejiang, 315211, China
| | - Wen-Hui Yang
- School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, Zhejiang, 315211, China
| | - Wen-Chan Tian
- School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, Zhejiang, 315211, China
| | - Guo-Ping Ge
- School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, Zhejiang, 315211, China
| | - Long-Yong Xie
- College of Chemistry and Bioengineering, Hunan University of Science and Engineering, Yongzhou, Hunan, 425100, China
| | - Rongnan Yi
- Criminal Technology Department, Hunan Police Academy, Changsha, Hunan, 410138, China
| | - Wen-Ting Wei
- School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, Zhejiang, 315211, China
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21
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Khalifa M, Fahim JR, Allam AE, Shoman ME, El Zawily A, Kamel MS, Shimizu K, Attia EZ. Studies on the Nonalkaloidal Secondary Metabolites of Hippeastrum vittatum (L'Her.) Herb. Bulbs. ACS OMEGA 2023; 8:26749-26761. [PMID: 37546665 PMCID: PMC10398848 DOI: 10.1021/acsomega.2c07886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/10/2022] [Accepted: 07/06/2023] [Indexed: 08/08/2023]
Abstract
Sixteen chemically varied metabolites were isolated from the bulbs of Hippeastrum vittatum (L'Her.) Herb., including eight flavonoids [3'-methyl isoliquiritigenin (2), 7-hydroxyflavan (8), 7-hydroxyflavanone (9), 7-hydroxyflavan-3-ol (10), 7-methoxy-3',4'-methylenedioxyflavan-3-ol (11), 7-hydroxy-3',4'-methylenedioxy flavan (12), 2',4'-dihydroxy-3'-methyl-3,4-methylenedioxychalcone (13), and isoliquiritigenin (14)], four acetophenones [2,6-dimethoxy-4-hydroxyacetophenone (3), 2,4-dihydroxyacetophenone (4), 2,4-dihydroxy-6-methoxy-3-methylacetophenone (6), and 2,4,6-trimethoxyacetophenone (7)], two alkaloids [lycorine (1) and narciprimine (15)], one phenol derivative [p-nitrophenol (5)], and one steroid [β-sitosterol 3-O-β-glucopyranoside (16)]. Their structures were elucidated by combining one- and two-dimensional NMR and ESI-MS techniques and by comparison with the reported literature data and some authentic samples. Except for lycorine (1), the isolated metabolites were obtained herein for the first time from Hippeastrum plants, among which compound 13 was identified as a new chalcone derivative. Additionally, the total phenolic and flavonoid contents of the total ethanol extract and different fractions of the bulbs were determined by the Folin-Ciocalteu and aluminum chloride colorimetric methods, respectively, whereas their antioxidant potential was compared using the phosphomolybdenum and 2,2'-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assays. Finally, the binding affinities of compounds 1-16 to some key target proteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), namely, main protease (Mpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp), were screened and compared using molecular docking analysis. The possible chemotaxonomic significance of the identified metabolites was also discussed.
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Affiliation(s)
- Marwa
Fathy Khalifa
- Department
of Pharmacognosy, Faculty of Pharmacy, Minia
University, 61519 Minia, Egypt
| | - John Refaat Fahim
- Department
of Pharmacognosy, Faculty of Pharmacy, Minia
University, 61519 Minia, Egypt
| | - Ahmed E. Allam
- Department
of Pharmacognosy, Faculty of Pharmacy, Al-Azhar
University, 71524 Assiut, Egypt
| | - Mai E. Shoman
- Department
of Medicinal Chemistry, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt
| | - Amr El Zawily
- Department
of Plant and Microbiology, Faculty of Science, Damanhour University, 22511 Damanhour, Egypt
- Department
of Biology, University of Iowa, Iowa City, Iowa 52242-1324, United
States
| | - Mohamed Salah Kamel
- Department
of Pharmacognosy, Faculty of Pharmacy, Minia
University, 61519 Minia, Egypt
| | - Kuniyoshi Shimizu
- Department
of Agro-Environmental Sciences, Graduate School of Bioresource and
Bioenvironmental Sciences, Kyushu University, 744 Motooka, Nishi-ku, 819-0395 Fukuoka, Japan
| | - Eman Zekry Attia
- Department
of Pharmacognosy, Faculty of Pharmacy, Minia
University, 61519 Minia, Egypt
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22
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He Y, Yang Z, Luo D, Luo X, Chen X, Yang W. An Oxidant-Free and Mild Strategy for Quinazolin-4(3 H)-One Synthesis via CuAAC/Ring Cleavage Reaction. Molecules 2023; 28:5734. [PMID: 37570705 PMCID: PMC10420183 DOI: 10.3390/molecules28155734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 07/21/2023] [Accepted: 07/26/2023] [Indexed: 08/13/2023] Open
Abstract
An oxidant-free and highly efficient synthesis of phenolic quinazolin-4(3H)-ones was achieved by simply stirring a mixture of 2-aminobenzamides, sulfonyl azides, and terminal alkynes. The intermediate N-sulfonylketenimine underwent two nucleophilic additions and the sulfonyl group eliminated through the power of aromatization. The natural product 2-(4-hydroxybenzyl)quinazolin-4(3H)-one can be synthesized on a large scale under mild conditions with this method.
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Affiliation(s)
- Yueling He
- The Marine Biomedical Research Institute of Guangdong Zhanjiang, Guangdong Medical University, Zhanjiang 524023, China; (Y.H.); (Z.Y.); (D.L.)
- School of Environmental Science and Engineering, Donghua University, Shanghai 201620, China
| | - Zhongtao Yang
- The Marine Biomedical Research Institute of Guangdong Zhanjiang, Guangdong Medical University, Zhanjiang 524023, China; (Y.H.); (Z.Y.); (D.L.)
| | - Danyang Luo
- The Marine Biomedical Research Institute of Guangdong Zhanjiang, Guangdong Medical University, Zhanjiang 524023, China; (Y.H.); (Z.Y.); (D.L.)
| | - Xiai Luo
- The Marine Biomedical Research Institute of Guangdong Zhanjiang, Guangdong Medical University, Zhanjiang 524023, China; (Y.H.); (Z.Y.); (D.L.)
- Hunan Province Key Laboratory for Synthetic Biology of Traditional Chinese Medicine, School of Pharmaceutical Sciences, Hunan University of Medicine, Huaihua 418000, China
| | - Xiaodong Chen
- Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang 524023, China
| | - Weiguang Yang
- The Marine Biomedical Research Institute of Guangdong Zhanjiang, Guangdong Medical University, Zhanjiang 524023, China; (Y.H.); (Z.Y.); (D.L.)
- Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang 524023, China
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23
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Parihar A, Malviya S, Khan R, Kaushik A, Mostafavi E. COVID-19 associated thyroid dysfunction and other comorbidities and its management using phytochemical-based therapeutics: a natural way. Biosci Rep 2023; 43:BSR20230293. [PMID: 37212057 PMCID: PMC10372472 DOI: 10.1042/bsr20230293] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 05/16/2023] [Accepted: 05/19/2023] [Indexed: 05/23/2023] Open
Abstract
The present severe acute respiratory syndrome-2 (SARS-CoV-2) mediated Coronavirus pandemic (COVID-19) and post-COVID-19 complications affect human life drastically. Patients who have been cured of COVID-19 infection are now experiencing post-COVID-19 associated comorbidities, which have increased mortality rates. The SARS-CoV-2 infection distresses the lungs, kidneys, gastrointestinal tract, and various endocrine glands, including the thyroid. The emergence of variants which includes Omicron (B.1.1.529) and its lineages threaten the world severely. Among different therapeutic approaches, phytochemical-based therapeutics are not only cost-effective but also have lesser side effects. Recently a plethora of studies have shown the therapeutic efficacy of various phytochemicals for the treatment of COVID-19. Besides this, various phytochemicals have been found efficacious in treating several inflammatory diseases, including thyroid-related anomalies. The method of the phytochemical formulation is quick and facile and the raw materials for such herbal preparations are approved worldwide for human use against certain disease conditions. Owing to the advantages of phytochemicals, this review primarily discusses the COVID-19-related thyroid dysfunction and the role of key phytochemicals to deal with thyroid anomaly and post-COVID-19 complications. Further, this review shed light on the mechanism via which COVID-19 and its related complication affect organ function of the body, along with the mechanistic insight into the way by which phytochemicals could help to cure post-COVID-19 complications in thyroid patients. Considering the advantages offered by phytochemicals as a safer and cost-effective medication they can be potentially used to combat COVID-19-associated comorbidities.
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Affiliation(s)
- Arpana Parihar
- Industrial Waste Utilization, Nano and Biomaterials, CSIR-Advanced Materials and Processes Research Institute (AMPRI), Hoshangabad Road, Bhopal 462026, MP, India
| | - Shivani Malviya
- Department of Biochemistry and Genetics, Barkatullah University, Habib Ganj, Bhopal, Madhya Pradesh 462026, India
| | - Raju Khan
- Industrial Waste Utilization, Nano and Biomaterials, CSIR-Advanced Materials and Processes Research Institute (AMPRI), Hoshangabad Road, Bhopal 462026, MP, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Ajeet Kaushik
- NanoBioTech Laboratory, Department of Environmental Engineering, Florida Polytechnic University, Lakeland, FL 33805, U.S.A
- School of Engineering, University of Petroleum and Energy Studies, Dehradun 248007, India
| | - Ebrahim Mostafavi
- Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, U.S.A
- Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, U.S.A
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24
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Toigo L, Dos Santos Teodoro EI, Guidi AC, Gancedo NC, Petruco MV, Melo EB, Tonin FS, Fernandez-Llimos F, Chierrito D, de Mello JCP, de Medeiros Araújo DC, Sanches ACC. Flavonoid as possible therapeutic targets against COVID-19: a scoping review of in silico studies. Daru 2023; 31:51-68. [PMID: 37195402 PMCID: PMC10191091 DOI: 10.1007/s40199-023-00461-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 04/25/2023] [Indexed: 05/18/2023] Open
Abstract
OBJECTIVES This scoping review aims to present flavonoid compounds' promising effects and possible mechanisms of action on potential therapeutic targets in the SARS-CoV-2 infection process. METHODS A search of electronic databases such as PubMed and Scopus was carried out to evaluate the performance of substances from the flavonoid class at different stages of SARS-CoV-2 infection. RESULTS The search strategy yielded 382 articles after the exclusion of duplicates. During the screening process, 265 records were deemed as irrelevant. At the end of the full-text appraisal, 37 studies were considered eligible for data extraction and qualitative synthesis. All the studies used virtual molecular docking models to verify the affinity of compounds from the flavonoid class with crucial proteins in the replication cycle of the SARS-CoV-2 virus (Spike protein, PLpro, 3CLpro/ MPro, RdRP, and inhibition of the host's ACE II receptor). The flavonoids with more targets and lowest binding energies were: orientin, quercetin, epigallocatechin, narcissoside, silymarin, neohesperidin, delphinidin-3,5-diglucoside, and delphinidin-3-sambubioside-5-glucoside. CONCLUSION These studies allow us to provide a basis for in vitro and in vivo assays to assist in developing drugs for the treatment and prevention of COVID-19.
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Affiliation(s)
- Larissa Toigo
- Centro de Ciências Médicas e Farmacêuticas, Universidade Estadual do Oeste do Paraná, Cascavel, Brazil
| | | | - Ana Carolina Guidi
- Laboratório de Biologia Farmacêutica, Departamento de Farmácia, Universidade Estadual de Maringá, Maringá, Brazil
| | - Naiara Cássia Gancedo
- Laboratório de Biologia Farmacêutica, Departamento de Farmácia, Universidade Estadual de Maringá, Maringá, Brazil
| | - Marcus Vinícius Petruco
- Clínica de Reumatologia-Pneumologia Laboratório do Sono de Maringá e Hospital Bom Samaritano de Maringá, Maringá, Brazil
| | - Eduardo Borges Melo
- Centro de Ciências Médicas e Farmacêuticas, Universidade Estadual do Oeste do Paraná, Cascavel, Brazil
| | - Fernanda Stumpf Tonin
- Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Paraná, Curitiba, Brazil
- H&TRC- Health & Technology Research Center, ESTeSLEscola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, Lisboa, Portugal
| | | | - Danielly Chierrito
- Centro de Ciências Médicas e Farmacêuticas, Universidade Estadual do Oeste do Paraná, Cascavel, Brazil
- Centro Universitário Ingá - UNINGÁ, Maringá, Brazil
| | - João Carlos Palazzo de Mello
- Laboratório de Biologia Farmacêutica, Departamento de Farmácia, Universidade Estadual de Maringá, Maringá, Brazil
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25
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Ksouri A, Klouz A, Bouhaouala-Zahar B, Moussa F, Bezzarga M. Docking-Based Evidence for the Potential of ImmunoDefender: A Novel Formulated Essential Oil Blend Incorporating Synergistic Antiviral Bioactive Compounds as Promising Mpro Inhibitors against SARS-CoV-2. Molecules 2023; 28:molecules28114296. [PMID: 37298772 DOI: 10.3390/molecules28114296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2023] [Revised: 05/14/2023] [Accepted: 05/16/2023] [Indexed: 06/12/2023] Open
Abstract
Essential oils (Eos) have demonstrated antiviral activity, but their toxicity can hinder their use as therapeutic agents. Recently, some essential oil components have been used within safe levels of acceptable daily intake limits without causing toxicity. The "ImmunoDefender," a novel antiviral compound made from a well-known mixture of essential oils, is considered highly effective in treating SARS-CoV-2 infections. The components and doses were chosen based on existing information about their structure and toxicity. Blocking the main protease (Mpro) of SARS-CoV-2 with high affinity and capacity is critical for inhibiting the virus's pathogenesis and transmission. In silico studies were conducted to examine the molecular interactions between the main essential oil components in "ImmunoDefender" and SARS-CoV-2 Mpro. The screening results showed that six key components of ImmunoDefender formed stable complexes with Mpro via its active catalytic site with binding energies ranging from -8.75 to -10.30 kcal/mol, respectively for Cinnamtannin B1, Cinnamtannin B2, Pavetannin C1, Syzyginin B, Procyanidin C1, and Tenuifolin. Furthermore, three essential oil bioactive inhibitors, Cinnamtannin B1, Cinnamtannin B2, and Pavetannin C, had significant ability to bind to the allosteric site of the main protease with binding energies of -11.12, -10.74, and -10.79 kcal/mol; these results suggest that these essential oil bioactive compounds may play a role in preventing the attachment of the translated polyprotein to Mpro, inhibiting the virus's pathogenesis and transmission. These components also had drug-like characteristics similar to approved and effective drugs, suggesting that further pre-clinical and clinical studies are needed to confirm the generated in silico outcomes.
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Affiliation(s)
- Ayoub Ksouri
- Laboratoire des Biomolécules, Venins et Applications Théranostiques, Institut Pasteur de Tunis, Université Tunis El Manar, 13 Place Pasteur, BP74, Tunis 1002, Tunisia
| | - Anis Klouz
- Faculté de Médecine de Tunis, Université Tunis El Manar, 15 Rue Djebel Lakhdhar, La Rabta, Tunis 1007, Tunisia
| | - Balkiss Bouhaouala-Zahar
- Laboratoire des Biomolécules, Venins et Applications Théranostiques, Institut Pasteur de Tunis, Université Tunis El Manar, 13 Place Pasteur, BP74, Tunis 1002, Tunisia
- Faculté de Médecine de Tunis, Université Tunis El Manar, 15 Rue Djebel Lakhdhar, La Rabta, Tunis 1007, Tunisia
| | - Fathi Moussa
- Institute of Physical Chemistry, CNRS-UMR 8000, University Paris-Saclay, Rue Noetzlin, 91190 Gif-sur-Yvette, France
| | - Mounir Bezzarga
- Laboratoire de Modélisation Mathématique, Faculté des Sciences de Tunis, Université Tunis El Manar, Analyse Harmonique et Théorie du Potentiel, Campus Universitaire, Tunis 1068, Tunisia
- Institut Préparatoire aux Etudes d'Ingénieurs de Tunis, Université de Tunis, Tunis 1068, Tunisia
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26
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Pal T, Anand U, Sikdar Mitra S, Biswas P, Tripathi V, Proćków J, Dey A, Pérez de la Lastra JM. Harnessing and bioprospecting botanical-based herbal medicines against potential drug targets for COVID-19: a review coupled molecular docking studies. J Biomol Struct Dyn 2023:1-23. [PMID: 37105230 DOI: 10.1080/07391102.2023.2187634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/29/2023]
Abstract
Since the end of February 2020, the world has come to a standstill due to the virus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). Since then, the global scientific community has explored various remedies and treatments against this virus, including natural products that have always been a choice because of their many benefits. Various known phytochemicals are well documented for their antiviral properties. Research is being carried out to discover new natural plant products or existing ones as a treatment measure for this disease. The three important targets in this regard are-papain like protease (PLpro), spike protein, and 3 chymotrypsin like proteases (3CLpro). Various docking studies are also being elucidated to identify the phytochemicals that modulate crucial proteins of the virus. The paper is simultaneously a comprehensive review that covers recent advances in the domain of the effect of various botanically derived natural products as an alternative treatment approach against Coronavirus Disease 2019 (COVID-19). Furthermore, the docking analyses revealed that rutin (inhibitor of the major protease of SARS-CoV-2), gallocatechin (e.g., interacting with 03 hydrogen bonds with a spike-like protein), lycorine (showing the best binding affinity with amino acids GLN498, THR500 and GLY446 of the spike-like protein), and quercetrin (inhabiting at its residues ASP216, PHE219, and ILE259) are promising inhibitors of SARS‑CoV‑2.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Tarun Pal
- Zuckerberg Institute for Water Research, Jacob Blaustein Institutes for Desert Research, Ben-Gurion University of the Negev, Sede Boqer Campus, Midreshet Ben-Gurion, Israel
| | | | - Shreya Sikdar Mitra
- Department of Life Sciences, Presidency University, Kolkata, West Bengal, India
| | - Protha Biswas
- Department of Life Sciences, Presidency University, Kolkata, West Bengal, India
| | - Vijay Tripathi
- Department of Molecular and Cellular Engineering, Jacob Institute of Biotechnology and Bioengineering, Sam Higginbottom University of Agriculture, Technology and Sciences, Prayagraj, Uttar Pradesh, India
| | - Jarosław Proćków
- Department of Plant Biology, Institute of Environmental Biology, Wrocław University of Environmental and Life Sciences, Wrocław, Poland
| | - Abhijit Dey
- Department of Life Sciences, Presidency University, Kolkata, West Bengal, India
| | - José M Pérez de la Lastra
- Biotechnology of Macromolecules Research Group, Instituto de Productos Naturales y Agrobiología, IPNA-CSIC, Tenerife, Spain
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27
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Hasan TN, Naqvi SS, Rehman MU, Ullah R, Ammad M, Arshad N, Ain QU, Perween S, Hussain A. Ginger ring compounds as an inhibitor of spike binding protein of alpha, beta, gamma and delta variants of SARS-CoV-2: An in-silico study. NARRA J 2023; 3:e98. [PMID: 38455706 PMCID: PMC10919719 DOI: 10.52225/narra.v3i1.98] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Accepted: 02/01/2023] [Indexed: 03/09/2024]
Abstract
The available drugs against coronavirus disease 2019 (COVOD-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are limited. This study aimed to identify ginger-derived compounds that might neutralize SARS-CoV-2 and prevent its entry into host cells. Ring compounds of ginger were screened against spike (S) protein of alpha, beta, gamma, and delta variants of SARS-CoV-2. The S protein FASTA sequence was retrieved from Global Initiative on Sharing Avian Influenza Data (GISAID) and converted into ".pdb" format using Open Babel tool. A total of 306 compounds were identified from ginger through food and phyto-databases. Out of those, 38 ring compounds were subjected to docking analysis using CB Dock online program which implies AutoDock Vina for docking. The Vina score was recorded, which reflects the affinity between ligands and receptors. Further, the Protein Ligand Interaction Profiler (PLIP) program for detecting the type of interaction between ligand-receptor was used. SwissADME was used to compute druglikeness parameters and pharmacokinetics characteristics. Furthermore, energy minimization was performed by using Swiss PDB Viewer (SPDBV) and energy after minimization was recorded. Molecular dynamic simulation was performed to find the stability of protein-ligand complex and root-mean- square deviation (RMSD) as well as root-mean-square fluctuation (RMSF) were calculated and recorded by using myPresto v5.0. Our study suggested that 17 out of 38 ring compounds of ginger were very likely to bind the S protein of SARS-CoV-2. Seventeen out of 38 ring compounds showed high affinity of binding with S protein of alpha, beta, gamma, and delta variants of SARS-CoV-2. The RMSD showed the stability of the complex was parallel to the S protein monomer. These computer-aided predictions give an insight into the possibility of ginger ring compounds as potential anti-SARS-CoV-2 worthy of in vitro investigations.
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Affiliation(s)
- Tarique N. Hasan
- Pure Health Laboratory, Mafraq Hospital, Abu Dhabi, United Arab Emirates
- School of Life Sciences, Manipal Academy of Higher Education, Dubai, United Arab Emirates
| | - Syed S. Naqvi
- Pure Health Laboratory, Mafraq Hospital, Abu Dhabi, United Arab Emirates
| | - Mati Ur Rehman
- Pure Health Laboratory, Mafraq Hospital, Abu Dhabi, United Arab Emirates
- College de Paris, France
| | - Rooh Ullah
- Pure Health Laboratory, Mafraq Hospital, Abu Dhabi, United Arab Emirates
| | - Muhammad Ammad
- Pure Health Laboratory, Mafraq Hospital, Abu Dhabi, United Arab Emirates
| | - Narmeen Arshad
- Pure Health Laboratory, Mafraq Hospital, Abu Dhabi, United Arab Emirates
| | - Qurat Ul Ain
- Pure Health Laboratory, Mafraq Hospital, Abu Dhabi, United Arab Emirates
| | - Shabana Perween
- Pure Health Laboratory, Mafraq Hospital, Abu Dhabi, United Arab Emirates
| | - Arif Hussain
- School of Life Sciences, Manipal Academy of Higher Education, Dubai, United Arab Emirates
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28
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Yang Z, Wu X, Zhang J, Yu JT, Pan C. Metal-Free Photoinduced Hydrocyclization of Unactivated Alkenes toward Ring-Fused Quinazolin-4(3 H)-ones via Intermolecular Hydrogen Atom Transfer. Org Lett 2023; 25:1683-1688. [PMID: 36883803 DOI: 10.1021/acs.orglett.3c00329] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/09/2023]
Abstract
A visible-light-induced hydrocyclization of unactivated alkenes was developed using 3CzClIPN as the photocatalyst to generate substituted α-methyldeoxyvasicinones and α-methylmackinazolinones in moderate to good yields. An intermolecular hydrogen atom transfer with THF as the hydrogen source was involved. Mechanism studies indicated that the intramolecular addition of the in situ formed aminal radical to the unactivated alkene generated the polycyclic quinazolinone.
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Affiliation(s)
- Zixian Yang
- School of Petrochemical Engineering, Changzhou University, Changzhou 213164, P. R. China
| | - Xian Wu
- School of Petrochemical Engineering, Changzhou University, Changzhou 213164, P. R. China
| | - Jie Zhang
- School of Petrochemical Engineering, Changzhou University, Changzhou 213164, P. R. China
| | - Jin-Tao Yu
- School of Petrochemical Engineering, Changzhou University, Changzhou 213164, P. R. China
| | - Changduo Pan
- School of Petrochemical Engineering, Changzhou University, Changzhou 213164, P. R. China.,School of Chemistry and Chemical Engineering, Jiangsu University of Technology, Changzhou 213001, P. R. China
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29
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Paul V, Tripathi AD, Agarwal A, Mahato DK, Srivastava K, Maurya KK. Herbs-derived phytochemicals - a boon for combating COVID-19. VEGETOS (BAREILLY, INDIA) 2023:1-8. [PMID: 37359125 PMCID: PMC10013230 DOI: 10.1007/s42535-023-00601-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 02/20/2023] [Accepted: 02/25/2023] [Indexed: 03/17/2023]
Abstract
The recent pandemic, the novel coronavirus (COVID-19), has put the whole world on alert with the threat of the virus that targets the human respiratory system. The disease has affected more than 633.6 million people globally and caused 6.5 million deaths since November 18, 2022. About 12.94 billion people are vaccinated as of November 18, 2022. Due to varied climatic conditions, SARS-CoV-2 has shown rapid mutation in recent years. Because of the lack of appropriate therapeutic drugs, inadequate diagnostic mechanisms, life-supporting medical facilities, and lack of awareness, the spread of SARS-CoV-2 has become severe. Thus, the most efficient strategy to control this disease is to follow preventive measures. However, treating SARS-CoV-2 cases in Wuhan using traditional Chinese herbs has set an example to show how traditional health can contribute to treating this novel virus. Medicinal herbs are known for their antimicrobial, antibacterial, antiviral, immunomodulatory, immunoadjuvant, and anti-inflammatory properties. These medicinal herbs are used during cooking and consumed regularly worldwide. In this view, medicinal herbs gained evident attention. These herbs can serve as a potential and economical remedy for combating the lethal effects of COVID-19. The present review highlights the phytochemicals and their mechanisms of action in preventing SARS-CoV-2. Supplementary Information The online version contains supplementary material available at 10.1007/s42535-023-00601-9.
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Affiliation(s)
- Veena Paul
- Department of Dairy Science and Food Technology, Institute of Agricultural Sciences, Banaras Hindu University, Varanasi, 221005 India
| | - Abhishek Dutt Tripathi
- Department of Dairy Science and Food Technology, Institute of Agricultural Sciences, Banaras Hindu University, Varanasi, 221005 India
| | - Aparna Agarwal
- Department of Food & Nutrition and Food Technology, Lady Irwin College, Sikandra Road, New Delhi, 110001 India
| | - Dipendra Kumar Mahato
- CASS Food Research Centre, School of Exercise and Nutrition Sciences, Deakin University, Burwood, 3125 VIC Australia
| | - Kartikeya Srivastava
- Department of Plant Genetics and Plant Breeding, Institute of Agricultural Sciences, Banaras Hindu University, Varanasi, 221005 India
| | - Kamlesh Kumar Maurya
- Department of Dairy Science and Food Technology, Institute of Agricultural Sciences, Banaras Hindu University, Varanasi, 221005 India
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30
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Bhat SA, Hasan SK, Parray ZA, Siddiqui ZI, Ansari S, Anwer A, Khan S, Amir F, Mehmankhah M, Islam A, Minuchehr Z, Kazim SN. Potential antiviral activities of chrysin against hepatitis B virus. Gut Pathog 2023; 15:11. [PMID: 36895013 PMCID: PMC9995728 DOI: 10.1186/s13099-023-00531-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 01/26/2023] [Indexed: 03/11/2023] Open
Abstract
BACKGROUND Interferon and nucleos(t)ide analogues are current therapeutic treatments for chronic Hepatitis B virus (HBV) infection with the limitations of a functional cure. Chrysin (5, 7-dihydroxyflavone) is a natural flavonoid, known for its antiviral and hepatoprotective activities. However, its anti-HBV activity is unexplored. METHODS In the present study, the anti-hepatitis B activity of chrysin was investigated using the in vitro experimental cell culture model, HepG2 cells. In silico studies were performed where chrysin and lamivudine (used here as a positive control) were docked with high mobility group box 1 protein (HMGB1). For the in vitro studies, wild type HBV genome construct (pHBV 1.3X) was transiently transfected in HepG2. In culture supernatant samples, HBV surface antigen (HBsAg) and Hepatitis B e antigen (HBeAg) were measured by enzyme-linked immunosorbent assay (ELISA). Secreted HBV DNA and intracellular covalently closed circular DNA (cccDNA) were measured by SYBR green real-time PCR. The 3D crystal structure of HMGB1 (1AAB) protein was developed and docked with the chrysin and lamivudine. In silico drug-likeness, Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties of finest ligands were performed by using SwissADME and admetSAR web servers. RESULTS Data showed that chrysin significantly decreases HBeAg, HBsAg secretion, supernatant HBV DNA and cccDNA, in a dose dependent manner. The docking studies demonstrated HMGB1 as an important target for chrysin as compared to lamivudine. Chrysin revealed high binding affinity and formed a firm kissing complex with HMGB1 (∆G = - 5.7 kcal/mol), as compared to lamivudine (∆G = - 4.3 kcal/mol), which might be responsible for its antiviral activity. CONCLUSIONS The outcome of our study establishes chrysin as a new antiviral against HBV infection. However, using chrysin to treat chronic HBV disease needs further endorsement and optimization by in vivo studies in animal models.
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Affiliation(s)
- Sajad Ahmad Bhat
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India
| | - Syed Kazim Hasan
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India
| | - Zahoor Ahmad Parray
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India
| | - Zaheenul Islam Siddiqui
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India
| | - Shabnam Ansari
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India
- Department of Biotechnology, Jamia Millia Islamia, New Delhi, India
| | - Ayesha Anwer
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India
| | - Saniya Khan
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India
| | - Fatima Amir
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India
- Department of Biosciences, Jamia Millia Islamia, New Delhi, India
| | - Mahboubeh Mehmankhah
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India
| | - Asimul Islam
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India
| | - Zarrin Minuchehr
- National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
| | - Syed Naqui Kazim
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India.
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31
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Purwaningsih I, Maksum IP, Sumiarsa D, Sriwidodo S. A Review of Fibraurea tinctoria and Its Component, Berberine, as an Antidiabetic and Antioxidant. Molecules 2023; 28:1294. [PMID: 36770960 PMCID: PMC9919506 DOI: 10.3390/molecules28031294] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 01/25/2023] [Accepted: 01/27/2023] [Indexed: 01/31/2023] Open
Abstract
Diabetes mellitus is a group of metabolic disorders characterized by hyperglycemia caused by resistance to insulin action, inadequate insulin secretion, or excessive glucagon production. Numerous studies have linked diabetes mellitus and oxidative stress. People with diabetes usually exhibit high oxidative stress due to persistent and chronic hyperglycemia, which impairs the activity of the antioxidant defense system and promotes the formation of free radicals. Recently, several studies have focused on exploring natural antioxidants to improve diabetes mellitus. Fibraurea tinctoria has long been known as the native Borneo used in traditional medicine to treat diabetes. Taxonomically, this plant is part of the Menispermaceae family, widely known for producing various alkaloids. Among them are protoberberine alkaloids such as berberine. Berberine is an isoquinoline alkaloid with many pharmacological activities. Berberine is receiving considerable interest because of its antidiabetic and antioxidant activities, which are based on many biochemical pathways. Therefore, this review explores the pharmacological effects of Fibraurea tinctoria and its active constituent, berberine, against oxidative stress and diabetes, emphasizing its mechanistic aspects. This review also summarizes the pharmacokinetics and toxicity of berberine and in silico studies of berberine in several diseases and its protein targets.
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Affiliation(s)
- Indah Purwaningsih
- Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Padjadjaran, Sumedang 45363, Indonesia
- Department of Medical Laboratory Technology, Poltekkes Kemenkes Pontianak, Pontianak 78124, Indonesia
| | - Iman Permana Maksum
- Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Padjadjaran, Sumedang 45363, Indonesia
| | - Dadan Sumiarsa
- Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Padjadjaran, Sumedang 45363, Indonesia
| | - Sriwidodo Sriwidodo
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia
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Preparation of Tryptanthrin Derivates Bearing a Thiosemicarbazone Moiety to Inhibit SARS-CoV-2 Replication. SEPARATIONS 2023. [DOI: 10.3390/separations10020073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
SARS-CoV-2 is a serious viral pathogen, and agents that inhibit its replication are in high demand. In the present work, we prepared two novel tryptanthrin derivates bearing a thiosemicarbazone moiety as potential antiviral agents. Both compounds displayed potent chelation activity against Fe(III/II) ion-associated COVID-19. The molecular docking results suggest that the compounds can display significant affinity towards SARS-CoV-2 papain-like proteases and SARS-CoV-2 main proteases. In addition, administering T8H-TSC can repress viral replication in the used model (Vero cells). Moreover, the therapeutic potential of the prepared compounds was predicted and analysed in terms of Lipinski’s rules, drug-likeness and drug score.
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Shokry S, Hegazy A, Abbas AM, Mostafa I, Eissa IH, Metwaly AM, Yahya G, El-Shazly AM, Aboshanab KM, Mostafa A. Phytoestrogen β-Sitosterol Exhibits Potent In Vitro Antiviral Activity against Influenza A Viruses. Vaccines (Basel) 2023; 11:228. [PMID: 36851106 PMCID: PMC9964242 DOI: 10.3390/vaccines11020228] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 01/14/2023] [Accepted: 01/17/2023] [Indexed: 01/22/2023] Open
Abstract
Influenza is a contagious infection in humans that is caused frequently by low pathogenic seasonal influenza viruses and occasionally by pathogenic avian influenza viruses (AIV) of H5, H7, and H9 subtypes. Recently, the clinical sector in poultry and humans has been confronted with many challenges, including the limited number of antiviral drugs and the rapid evolution of drug-resistant variants. Herein, the anti-influenza activities of various plant-derived phytochemicals were investigated against highly pathogenic avian influenza A/H5N1 virus (HPAIV H5N1) and seasonal low pathogenic human influenza A/H1N1 virus (LPHIV H1N1). Out of the 22 tested phytochemicals, the steroid compounds β-sitosterol and β-sitosterol-O-glucoside have very potent activity against the predefined influenza A viruses (IAV). Both steroids could induce such activity by affecting multiple stages during IAV replication cycles, including viral adsorption and replication with a major and significant impact on the virus directly in a cell-free status "viricidal effect". On a molecular level, several molecular docking studies suggested that β-sitosterol and β-sitosterol-O-glucoside exhibited viricidal effects through blocking active binding sites of the hemagglutinin surface protein, as well as showing inhibitory effects against replication through the binding with influenza neuraminidase activity and blocking the active sites of the M2 proton channel activity. The phytoestrogen β-sitosterol has structural similarity with the active form of the female sex hormone estradiol, and this similarity is likely one of the molecular determinants that enables the phytoestrogen β-sitosterol and its derivative to control IAV infection in vitro. This promising anti-influenza activity of β-sitosterol and its O-glycoside derivative, according to both in vitro and cheminformatics studies, recommend both phytochemicals for further studies going through preclinical and clinical phases as efficient anti-influenza drug candidates.
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Affiliation(s)
- Sara Shokry
- Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt
- Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo 11566, Egypt
| | - Akram Hegazy
- Department of Agricultural Microbiology, Faculty of Agriculture, Cairo University, Giza District, Giza 12613, Egypt
| | - Ahmad M. Abbas
- Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo 11566, Egypt
- Department of Microbiology and Immunology, Faculty of Pharmacy, King Salman International University (KSIU), Sinai 46612, Egypt
| | - Islam Mostafa
- Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
| | - Ibrahim H. Eissa
- Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt
| | - Ahmed M. Metwaly
- Pharmacognosy and Medicinal Plants Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt
- Biopharmaceutical Products Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications (SRTA-City), Alexandria 21934, Egypt
| | - Galal Yahya
- Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
| | - Assem M. El-Shazly
- Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
- Faculty of Pharmacy, El Saleheya El Gadida University, El Saleheya El Gadida 44813, Sharkia, Egypt
| | - Khaled M. Aboshanab
- Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo 11566, Egypt
| | - Ahmed Mostafa
- Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt
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Ashoka GB, Shivanna MB. Metabolite profiling, in vitro and in silico assessment of antibacterial and anticancer activities of Alternaria alternata endophytic in Jatropha heynei. Arch Microbiol 2023; 205:61. [PMID: 36625985 DOI: 10.1007/s00203-022-03388-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 12/09/2022] [Accepted: 12/22/2022] [Indexed: 01/11/2023]
Abstract
Fungal endophytes produce a range of structurally diverse metabolites with bioactive principles. In this study, an endophytic fungus Alternaria alternata was isolated from Jatropha heynei and cultured in potato dextrose liquid broth. Culture filtrate of A. alternata was extracted in ethyl acetate and metabolites were characterized by QTOF-HRLCMS. Among compounds detected, spectral compounds such as kigelinone, and levofuraltadone were reported with antibacterial property, while 2-hydroxychrasophanol, isoathyriol, glycophymoline, columbianetin and kaempferol 3-O-β-D- galactoside were reported with cytotoxic properties. Partially purified metabolites of A. alternata showed significant antibacterial activity against tested clinical bacterial strains by agar well diffusion method. High zone of inhibition was recorded against Enterococcus faecalis, Pseudomonas syringae and Klebsiella pneumoniae. In vitro anticancer activity of fungal extract by MTT assay displayed high cytotoxic effect on human lung carcinoma cancer cell line (A549) with IC50 value of 393.52 µg ml-1, and without any significant cytotoxic effect on human breast cancer cell line (MCF-7). Further, antibacterial and anticancer spectral compounds of A. alternata were subjected to molecular docking analysis with antibacterial target proteins such as tellurite resistance protein (2JXU), indole-3-acetaldehyde dehydrogenase (5IUU) and alkyl hydroperoxide reductase (5Y63), and anticancer target human apoptotic regulator protein (1G5M). The results of the study indicated that kigelinone, levofuraltadone, 2-hydroxychrasophanol and isoathyriol in the fungal extract have significant binding modes, with best binding energy scores with their respective antibacterial and anticancer target proteins. Alternaria alternata resident in J. heynei offers a promising source of broad-spectrum antibacterial and anticancer compounds.
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Affiliation(s)
- Gowdru Basanna Ashoka
- Department of P.G. Studies and Research in Applied Botany, School of Biosciences, Kuvempu University, Jnana Sahyadri, Shankaraghatta, 577451, Shivamogga, India
| | - Manchanahally Byrappa Shivanna
- Department of P.G. Studies and Research in Applied Botany, School of Biosciences, Kuvempu University, Jnana Sahyadri, Shankaraghatta, 577451, Shivamogga, India.
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Elmi A, Mohamed AS, Said S, Bationo R. A Comparison Study of Medicinal Plants Used Against SARS-CoV-2 and Those Recommended Against Malaria in Africa. ETHNOPHARMACOLOGY AND DRUG DISCOVERY FOR COVID-19: ANTI-SARS-COV-2 AGENTS FROM HERBAL MEDICINES AND NATURAL PRODUCTS 2023:549-573. [DOI: 10.1007/978-981-99-3664-9_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Babalghith AO, Al-kuraishy HM, Al-Gareeb AI, De Waard M, Al-Hamash SM, Jean-Marc S, Negm WA, Batiha GES. The role of berberine in Covid-19: potential adjunct therapy. Inflammopharmacology 2022; 30:2003-2016. [PMID: 36183284 PMCID: PMC9526677 DOI: 10.1007/s10787-022-01080-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Accepted: 09/09/2022] [Indexed: 12/16/2022]
Abstract
Coronavirus disease 2019 (Covid-19) is a global diastrophic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Covid-19 leads to inflammatory, immunological, and oxidative changes, by which SARS-CoV-2 leads to endothelial dysfunction (ED), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and multi-organ failure (MOF). Despite evidence illustrating that some drugs and vaccines effectively manage and prevent Covid-19, complementary herbal medicines are urgently needed to control this pandemic disease. One of the most used herbal medicines is berberine (BBR), which has anti-inflammatory, antioxidant, antiviral, and immune-regulatory effects; thus, BBR may be a prospective candidate against SARS-CoV-2 infection. This review found that BBR has anti-SARS-CoV-2 effects with mitigation of associated inflammatory changes. BBR also reduces the risk of ALI/ARDS in Covid-19 patients by inhibiting the release of pro-inflammatory cytokines and inflammatory signaling pathways. In conclusion, BBR has potent anti-inflammatory, antioxidant, and antiviral effects. Therefore, it can be utilized as a possible anti-SARS-CoV-2 agent. BBR inhibits the proliferation of SARS-CoV-2 and attenuates the associated inflammatory disorders linked by the activation of inflammatory signaling pathways. Indeed, BBR can alleviate ALI/ARDS in patients with severe Covid-19. In this sense, clinical trials and prospective studies are suggested to illustrate the potential role of BBR in treating Covid-19.
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Affiliation(s)
- Ahmad O. Babalghith
- Medical Genetics Department, College of Medicine, Umm Al-Qura University, Mecca, Kingdom of Saudi Arabia
| | - Hayder M. Al-kuraishy
- Department of Clinical Pharmacology and Medicine, College of Medicine, ALmustansiriyia University, Baghdad, Iraq
| | - Ali I. Al-Gareeb
- Department of Clinical Pharmacology and Medicine, College of Medicine, ALmustansiriyia University, Baghdad, Iraq
| | - Michel De Waard
- Smartox Biotechnology, 6 rue des Platanes, 38120 Saint-Egrève, France
- L’institut du Thorax, INSERM, CNRS, UNIV NANTES, 44007 Nantes, France
- LabEx « Ion Channels, Science and Therapeutics», Université de Nice Sophia-Antipolis, 06560 Valbonne, France
| | - Sadiq Mohammed Al-Hamash
- Department of Clinical Pharmacology and Medicine, College of Medicine, ALmustansiriyia University, Baghdad, Iraq
| | - Sabatier Jean-Marc
- Faculté des sciences médicales et paramédicales, Aix-Marseille Université, Institut de Neurophysiopathologie (INP), CNRS UMR, 7051, 27 Bd Jean Moulin, 13005 Marseille, France
| | - Walaa A. Negm
- Department of Pharmacognosy, Faculty of Pharmacy, Tanta University, Tanta, 31527 Egypt
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511 Al Beheira Egypt
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Chauhan S, Saini D, Madan K. Screening of Phytoconstituents from Traditional Plants against SARSCoV-
2 using Molecular Docking Approach. LETT DRUG DES DISCOV 2022. [DOI: 10.2174/1570180819666220307163058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background:
The emergence of COVID-19 as a fatal viral disease encourages researchers to
develop effective and efficient therapeutic agents. The intervention of in silico studies has led to revolutionary
changes in the conventional method of testing the bioactivity of plant constituents.
Objective:
The current study deals with the investigation of some traditional immunomodulators of plant
origin to combat this ailment.
Materials and Methods:
A total of 151 phytomolecules of 12 immunomodulatory plants were evaluated
for their inhibitory action against the main protease (PDB ID: 7D1M) and NSP15 endoribonuclease (PDB
ID: 6WLC) by structure-based virtual screening. In addition, the promising molecules with ligand efficiency
of more than -0.3(kcal/mol)/heavy atoms were further predicted for pharmacokinetic properties
and druggability using the SwissADME web server, and their toxicity was also evaluated using Protox-II.
Result:
Myricetin-3-O-arabinofuranoside of cranberry plant was found to be the most potential candidate
against both enzymes: main protease (–14.2 kcal/mol) and NSP15 endoribonuclease (–12.2 kcal/mol).
Conclusion:
The promising outcomes of the current study may be implemented in future drug development
against coronavirus. The findings also help in the development of lead candidates of plant origin
with a better ADMET profile in the future.
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Affiliation(s)
- Shilpi Chauhan
- Department of Pharmacy, Lloyd Institute of Management and Technology, Plot No.-11, Knowledge Park-I1, Greater
Noida, Uttar Pradesh 201306, India
| | - Deepika Saini
- Department of Pharmacy, Lloyd Institute of Management and Technology, Plot No.-11, Knowledge Park-I1, Greater
Noida, Uttar Pradesh 201306, India
| | - Kumud Madan
- Department of Pharmacy, Lloyd Institute of Management and Technology, Plot No.-11, Knowledge Park-I1, Greater
Noida, Uttar Pradesh 201306, India
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Banerjee S, Baidya SK, Adhikari N, Ghosh B, Jha T. Glycyrrhizin as a promising kryptonite against SARS-CoV-2: Clinical, experimental, and theoretical evidences. J Mol Struct 2022; 1275:134642. [DOI: 10.1016/j.molstruc.2022.134642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Revised: 10/24/2022] [Accepted: 11/24/2022] [Indexed: 11/27/2022]
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Zhao Y, Deng S, Bai Y, Guo J, Kai G, Huang X, Jia X. Promising natural products against SARS-CoV-2: Structure, function, and clinical trials. Phytother Res 2022; 36:3833-3858. [PMID: 35932157 PMCID: PMC9538226 DOI: 10.1002/ptr.7580] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 07/04/2022] [Accepted: 07/07/2022] [Indexed: 01/18/2023]
Abstract
The corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus type 2 (SARS-COV-2) poses a severe threat to human health and still spreads globally. Due to the high mutation ratio and breakthrough infection rate of the virus, vaccines and anti-COVID-19 drugs require continual improvements. Drug screening research has shown that some natural active products can target the critical proteins of SARS-CoV-2, including 3CLpro, ACE2, FURIN, and RdRp, which could produce great inhibitory effects on SARS-COV-2. In addition, some natural products have displayed activities of immunomodulation, antiinflammatory, and antihepatic failure in COVID-19 clinical trials, which may relate to their non-monomeric structures. However, further evaluation and high-quality assessments, including safety verification tests, drug interaction tests, and clinical trials, are needed to substantiate natural products' multi-target and multi-pathway effects on COVID-19. Here, we review the literature on several promising active natural products that may act as vaccine immune enhancers or provide targeted anti-COVID-19 drugs. The structures, mechanisms of action, and research progress of these natural products are analyzed, to hopefully provide effective ideas for the development of targeted drugs that possess better structure, potency, and safety.
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Affiliation(s)
- Yan Zhao
- Life Science and EngineeringSouthwest Jiaotong UniversityChengduChina
| | - Shanshan Deng
- Sichuan Key Laboratory of Noncoding RNA and DrugsChengdu Medical CollegeChengduChina
| | - Yujiao Bai
- Sichuan Key Laboratory of Noncoding RNA and DrugsChengdu Medical CollegeChengduChina
| | - Jinlin Guo
- Key Laboratory of Systematic Research of Distinctive Chinese Medicine Resources in Southwest ChinaChengdu University of Traditional Chinese MedicineChengduChina
| | - Guoyin Kai
- Zhejiang Chinese Medical UniversityHangzhouChina
| | - Xinhe Huang
- Life Science and EngineeringSouthwest Jiaotong UniversityChengduChina
| | - Xu Jia
- Sichuan Key Laboratory of Noncoding RNA and DrugsChengdu Medical CollegeChengduChina
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Mousavi S, Zare S, Mirzaei M, Feizi A. Novel Drug Design for Treatment of COVID-19: A Systematic Review of Preclinical Studies. THE CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY = JOURNAL CANADIEN DES MALADIES INFECTIEUSES ET DE LA MICROBIOLOGIE MEDICALE 2022; 2022:2044282. [PMID: 36199815 PMCID: PMC9527439 DOI: 10.1155/2022/2044282] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 05/23/2022] [Accepted: 08/03/2022] [Indexed: 11/27/2022]
Abstract
Background Since the beginning of the novel coronavirus (SARS-CoV-2) disease outbreak, there has been an increasing interest in discovering potential therapeutic agents for this disease. In this regard, we conducted a systematic review through an overview of drug development (in silico, in vitro, and in vivo) for treating COVID-19. Methods A systematic search was carried out in major databases including PubMed, Web of Science, Scopus, EMBASE, and Google Scholar from December 2019 to March 2021. A combination of the following terms was used: coronavirus, COVID-19, SARS-CoV-2, drug design, drug development, In silico, In vitro, and In vivo. A narrative synthesis was performed as a qualitative method for the data synthesis of each outcome measure. Results A total of 2168 articles were identified through searching databases. Finally, 315 studies (266 in silico, 34 in vitro, and 15 in vivo) were included. In studies with in silico approach, 98 article study repurposed drug and 91 studies evaluated herbal medicine on COVID-19. Among 260 drugs repurposed by the computational method, the best results were observed with saquinavir (n = 9), ritonavir (n = 8), and lopinavir (n = 6). Main protease (n = 154) following spike glycoprotein (n = 62) and other nonstructural protein of virus (n = 45) was among the most studied targets. Doxycycline, chlorpromazine, azithromycin, heparin, bepridil, and glycyrrhizic acid showed both in silico and in vitro inhibitory effects against SARS-CoV-2. Conclusion The preclinical studies of novel drug design for COVID-19 focused on main protease and spike glycoprotein as targets for antiviral development. From evaluated structures, saquinavir, ritonavir, eucalyptus, Tinospora cordifolia, aloe, green tea, curcumin, pyrazole, and triazole derivatives in in silico studies and doxycycline, chlorpromazine, and heparin from in vitro and human monoclonal antibodies from in vivo studies showed promised results regarding efficacy. It seems that due to the nature of COVID-19 disease, finding some drugs with multitarget antiviral actions and anti-inflammatory potential is valuable and some herbal medicines have this potential.
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Affiliation(s)
- Sarah Mousavi
- Department of Clinical Pharmacy and Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Shima Zare
- School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mahmoud Mirzaei
- Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Awat Feizi
- Department of Epidemiology and Biostatistics, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran
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Liu C, Puopolo T, Li H, Cai A, Seeram NP, Ma H. Identification of SARS-CoV-2 Main Protease Inhibitors from a Library of Minor Cannabinoids by Biochemical Inhibition Assay and Surface Plasmon Resonance Characterized Binding Affinity. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27186127. [PMID: 36144858 PMCID: PMC9502466 DOI: 10.3390/molecules27186127] [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] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 09/15/2022] [Accepted: 09/16/2022] [Indexed: 01/08/2023]
Abstract
The replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mediated by its main protease (Mpro), which is a plausible therapeutic target for coronavirus disease 2019 (COVID-19). Although numerous in silico studies reported the potential inhibitory effects of natural products including cannabis and cannabinoids on SARS-CoV-2 Mpro, their anti-Mpro activities are not well validated by biological experimental data. Herein, a library of minor cannabinoids belonging to several chemotypes including tetrahydrocannabinols, cannabidiols, cannabigerols, cannabichromenes, cannabinodiols, cannabicyclols, cannabinols, and cannabitriols was evaluated for their anti-Mpro activity using a biochemical assay. Additionally, the binding affinities and molecular interactions between the active cannabinoids and the Mpro protein were studied by a biophysical technique (surface plasmon resonance; SPR) and molecular docking, respectively. Cannabinoids tetrahydrocannabutol and cannabigerolic acid were the most active Mpro inhibitors (IC50 = 3.62 and 14.40 μM, respectively) and cannabigerolic acid had a binding affinity KD=2.16×10-4 M). A preliminary structure and activity relationship study revealed that the anti-Mpro effects of cannabinoids were influenced by the decarboxylation of cannabinoids and the length of cannabinoids' alkyl side chain. Findings from the biochemical, biophysical, and computational assays support the growing evidence of cannabinoids' inhibitory effects on SARS-CoV-2 Mpro.
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Affiliation(s)
- Chang Liu
- Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA
- Cannabis Research Collaborative, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA
| | - Tess Puopolo
- Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA
| | - Huifang Li
- Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA
| | - Ang Cai
- Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA
| | - Navindra P. Seeram
- Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA
- Cannabis Research Collaborative, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA
- Correspondence: (N.P.S.); (H.M.); Tel.: +1-(401)-874-9367 (N.P.S.); +1-(401)-874-2711 (H.M.)
| | - Hang Ma
- Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA
- Cannabis Research Collaborative, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA
- Correspondence: (N.P.S.); (H.M.); Tel.: +1-(401)-874-9367 (N.P.S.); +1-(401)-874-2711 (H.M.)
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In Silico Evaluation of Sesquiterpenes and Benzoxazinoids Phytotoxins against Mpro, RNA Replicase and Spike Protein of SARS-CoV-2 by Molecular Dynamics. Inspired by Nature. Toxins (Basel) 2022; 14:toxins14090599. [PMID: 36136537 PMCID: PMC9506577 DOI: 10.3390/toxins14090599] [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: 08/05/2022] [Revised: 08/25/2022] [Accepted: 08/26/2022] [Indexed: 11/17/2022] Open
Abstract
In the work described here, a number of sesquiterpenes and benzoxazinoids from natural sources, along with their easily accessible derivatives, were evaluated against the main protease, RNA replicase and spike glycoprotein of SARS-CoV-2 by molecular docking. These natural products and their derivatives have previously shown remarkable antiviral activities. The most relevant compounds were the 4-fluoro derivatives of santamarine, reynosin and 2-amino-3H-phenoxazin-3-one in terms of the docking score. Those compounds fulfill the Lipinski’s rule, so they were selected for the analysis by molecular dynamics, and the kinetic stabilities of the complexes were assessed. The addition of the 4-fluorobenzoate fragment to the natural products enhances their potential against all of the proteins tested, and the complex stability after 50 ns validates the inhibition calculated. The derivatives prepared from reynosin and 2-amino-3H-phenoxazin-3-one are able to generate more hydrogen bonds with the Mpro, thus enhancing the stability of the protein–ligand and generating a long-term complex for inhibition. The 4-fluoro derivate of santamarine and reynosin shows to be really active against the spike protein, with the RMSD site fluctuation lower than 1.5 Å. Stabilization is mainly achieved by the hydrogen-bond interactions, and the stabilization is improved by the 4-fluorobenzoate fragment being added. Those compounds tested in silico reach as candidates from natural sources to fight this virus, and the results concluded that the addition of the 4-fluorobenzoate fragment to the natural products enhances their inhibition potential against the main protease, RNA replicase and spike protein of SARS-CoV-2.
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Wang Z, Belecciu T, Eaves J, Reimers M, Bachmann MH, Woldring D. Phytochemical drug discovery for COVID-19 using high-resolution computational docking and machine learning assisted binder prediction. J Biomol Struct Dyn 2022:1-21. [PMID: 35993534 DOI: 10.1080/07391102.2022.2112976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
Abstract
The COVID-19 pandemic has resulted in millions of deaths around the world. Multiple vaccines are in use, but there are many underserved locations that do not have adequate access to them. Variants may emerge that are highly resistant to existing vaccines, and therefore cheap and readily obtainable therapeutics are needed. Phytochemicals, or plant chemicals, can possibly be such therapeutics. Phytochemicals can be used in a polypharmacological approach, where multiple viral proteins are inhibited and escape mutations are made less likely. Finding the right phytochemicals for viral protein inhibition is challenging, but in-silico screening methods can make this a more tractable problem. In this study, we screen a wide range of natural drug products against a comprehensive set of SARS-CoV-2 proteins using a high-resolution computational workflow. This workflow consists of a structure-based virtual screening (SBVS), where an initial phytochemical library was docked against all selected protein structures. Subsequently, ligand-based virtual screening (LBVS) was employed, where chemical features of 34 lead compounds obtained from the SBVS were used to predict 53 lead compounds from a larger phytochemical library via supervised learning. A computational docking validation of the 53 predicted leads obtained from LBVS revealed that 28 of them elicit strong binding interactions with SARS-CoV-2 proteins. Thus, the inclusion of LBVS resulted in a 4-fold increase in the lead discovery rate. Of the total 62 leads, 18 showed promising pharmacokinetic properties in a computational ADME screening. Collectively, this study demonstrates the advantage of incorporating machine learning elements into a virtual screening workflow.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Zirui Wang
- Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA.,Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI, USA
| | - Theodore Belecciu
- Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA.,Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI, USA
| | - Joelle Eaves
- Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA.,Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI, USA
| | - Mark Reimers
- Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA.,Department of Biomedical Engineering, Michigan State University, East Lansing, MI, USA
| | - Michael H Bachmann
- Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA.,Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, USA
| | - Daniel Woldring
- Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA.,Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI, USA
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Sahoo R, Sahu P, Swargam S, Kumari I, Behera B. Repurposing small molecules of Tephrosia purpurea against SARS-CoV-2 main protease. J Biomol Struct Dyn 2022:1-12. [PMID: 35983619 DOI: 10.1080/07391102.2022.2112616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
Abstract
Coronavirus infection is a communicable disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged as a global pandemic with deteriorating effect on the world's population. Main protease (Mpro) of SARS-CoV-2 plays a significant role in the viral replication, transcription and disease propagation as well as a potential candidate for drug discovery and development for COVID-19 infection. The current study employed state of art structure-based drug discovery to decipher the role of phytochemicals of Tephrosia purpurea against Mpro. Tephrosia purpurea is being used as a traditional medicinal plant for the treatment of cough, breathlessness and fever as per the Indian Materia Medica. Screening of the phytochemicals of Tephrosia purpurea against Mpro was performed using molecular docking approach to identify the top 5 hits (+)-tephrorin B, deguelin, vitamin p, lanceolarin and 3beta-hydroxy-20(29)-lupene with binding energy of -8.4, -8.1, -8.0, -7.8, and -7.8 kcal/mol, respectively. Furthermore, identified top 5 hits were subjected to drug-likeness and toxicity prediction as well as MM-GBSA calculation. Out of the five molecules four molecules were predicted not to comprise any mutagenic and carcinogenic effects. Top two molecules based on the drug-likeness properties for oral bio-availability were further analysed by molecular dynamics simulation at 100 ns timescale. It was observed from the dynamic behaviour of the two complexes that the addition of these molecules changed the conformation and stability of the apo protein; thus may act as inhibitors for Mpro.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Rosaleen Sahoo
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India.,Biochemical Sciences Division, CSIR-National Chemical Laboratory, Pune, Maharashtra, India
| | - Parameswar Sahu
- Central Molecular Laboratory, Govind Ballabh Pant Institute of Postgraduate Medical Education & Research, New Delhi, India
| | - Sandeep Swargam
- Genomics and Epidemiology Division, National Centre for Disease Control, Civil Lines, New Delhi, India
| | - Indu Kumari
- Department of Environmental Sciences, Central University of Himachal Pradesh, Kangra, Himachal Pradesh, India
| | - Banshidhar Behera
- Department of Dravyaguna, Ayurvedic and Unani Tibbia College, New Delhi, India
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Yip KM, Lee KM, Ng TB, Xu S, Yung KKL, Qu S, Cheung AKL, Sze SCW. An anti-inflammatory and anti-fibrotic proprietary Chinese medicine nasal spray designated as Allergic Rhinitis Nose Drops (ARND) with potential to prevent SARS-CoV-2 coronavirus infection by targeting RBD (Delta)- angiotensin converting enzyme 2 (ACE2) binding. Chin Med 2022; 17:88. [PMID: 35897044 PMCID: PMC9328017 DOI: 10.1186/s13020-022-00635-2] [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: 01/18/2022] [Accepted: 06/18/2022] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND Since the outbreak of COVID-19 has resulted in over 313,000,000 confirmed cases of infection and over 5,500,000 deaths, substantial research work has been conducted to discover agents/ vaccines against COVID-19. Undesired adverse effects were observed in clinical practice and common vaccines do not protect the nasal tissue. An increasing volume of direct evidence based on clinical studies of traditional Chinese medicines (TCM) in the treatment of COVID-19 has been reported. However, the safe anti-inflammatory and anti-fibrotic proprietary Chinese medicines nasal spray, designated as Allergic Rhinitis Nose Drops (ARND), and its potential of re-purposing for suppressing viral infection via SARS-CoV-2 RBD (Delta)- angiotensin converting enzyme 2 (ACE2) binding have not been elucidated. PURPOSE To characterize ARND as a potential SARS-CoV-2 entry inhibitor for its possible preventive application in anti-virus hygienic agent. METHODS Network pharmacology analysis of ARND was adopted to asacertain gene targets which were commonly affected by COVID-19. The inhibitory effect of ARND on viral infection was determined by an in vitro pseudovirus assay. Furthermore, ARND was confirmed to have a strong binding affinity with ACE2 and SARS-CoV-2 spike-RBD (Delta) by ELISA. Finally, inflammatory and fibrotic cell models were used in conjunction in this study. RESULTS The results suggested ARND not only inhibited pseudovirus infection and undermined the binding affinity between ACE2 and the Spike protein (Delta), but also attenuated the inflammatory response upon infection and may lead to a better prognosis with a lower risk of pulmonary fibrosis. The data in this study also provide a basis for further development of ARND as an antiviral hygienic product and further investigations on ARND in the live virus, in vivo and COVID-19 patients. ARND holds promise for use in the current COVID-19 outbreak as well as in future pandemics. CONCLUSION ARND could be considered as a safe anti-SARS-CoV-2 agent with potential to prevent SARS-CoV-2 coronavirus infection.
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Affiliation(s)
- Ka Man Yip
- Department of Biology, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong, Special Administrative Region, China.,Golden Meditech Center for NeuroRegeneration Sciences, Hong Kong Baptist University, Kowloon Tong, Hong Kong, Special Administrative Region, China
| | - Kwan Ming Lee
- Department of Biology, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong, Special Administrative Region, China.,Golden Meditech Center for NeuroRegeneration Sciences, Hong Kong Baptist University, Kowloon Tong, Hong Kong, Special Administrative Region, China
| | - Tzi Bun Ng
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Region, China
| | - Shujun Xu
- Department of Biology, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong, Special Administrative Region, China.,Golden Meditech Center for NeuroRegeneration Sciences, Hong Kong Baptist University, Kowloon Tong, Hong Kong, Special Administrative Region, China
| | - Ken Kin Lam Yung
- Department of Biology, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong, Special Administrative Region, China. .,Golden Meditech Center for NeuroRegeneration Sciences, Hong Kong Baptist University, Kowloon Tong, Hong Kong, Special Administrative Region, China.
| | - Shaogang Qu
- Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China. .,Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangzhou, 510515, Guangdong, China. .,Key Laboratory of Mental Health of the Ministry of Education, Southern Medical University, Guangzhou, 510515, Guangdong, China.
| | - Allen Ka Loon Cheung
- Department of Biology, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong, Special Administrative Region, China.
| | - Stephen Cho Wing Sze
- Department of Biology, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong, Special Administrative Region, China. .,Golden Meditech Center for NeuroRegeneration Sciences, Hong Kong Baptist University, Kowloon Tong, Hong Kong, Special Administrative Region, China.
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Mu B, Zhang L, Lv G, Chen K, Wang T, Chen J, Huang T, Guo L, Yang Z, Wu Y. Access to Phosphine-Containing Quinazolinones Enabled by Photo-Induced Radical Phosphorylation/Cyclization of Unactivated Alkenes. J Org Chem 2022; 87:10146-10157. [PMID: 35830565 DOI: 10.1021/acs.joc.2c01092] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
A mild and facile photo-induced cascade radical addition/cyclization of unactivated alkenes has been reported, through which a variety of biologically valuable phosphine-containing quinazolinones could be obtained in moderate to good yields. The protocol was characterized by mild conditions, broad substrate scope, and high atomic economy.
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Affiliation(s)
- Binsong Mu
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Le Zhang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Guanghui Lv
- Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, No. 32 South Renmin Road, Shiyan, Huibei 442000, China
| | - Kang Chen
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Ting Wang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Jian Chen
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Tianle Huang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Li Guo
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Zhongzhen Yang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Yong Wu
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
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Antimicrobial Alkaloids from Marine-Derived Fungi as Drug Leads versus COVID-19 Infection: A Computational Approach to Explore their Anti-COVID-19 Activity and ADMET Properties. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:5403757. [PMID: 35911157 PMCID: PMC9325633 DOI: 10.1155/2022/5403757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 06/11/2022] [Indexed: 11/28/2022]
Abstract
Therapeutic strategies based upon enzyme inhibition have recently gained higher attention in treating hazardous ailments. Herein, the potential use of seventy-two antimicrobial alkaloids isolated from marine-derived fungi to fight COVID-19 infection via inhibition of SARS-CoV-2 lethal virus was performed using in silico analyses. Molecular modelling was performed to assess their enzyme inhibitory potential on the main protease SARS-CoV-2 MPro, 3-chymotrypsin-like protease SARS-CoV-2 3CLpro, and papain-like protease SARS-CoV-2 PLpro using Discovery Studio 4.5. Validation of the docking experiments was done by determination of RMSD (root mean square deviation) after redocking the superimposition of the cocrystalized ligands. Results showed that gymnastatin Z (72) showed the best fitting score in SARS-CoV-2 MPro and SARS-CoV-2 3CLpr active sites with ∆G equal −34.15 and −34.28 Kcal/mol, respectively. Meanwhile, scalusamide C (62) displayed the highest fitting within SARS-CoV-2 PLpro active sites (∆G = −26.91 Kcal/mol) followed by eutypellazine M (57). ADMET/TOPKAT prediction displayed that eutypellazine M and scalusamide C showed better pharmacokinetic and pharmacodynamic properties. Gymnastatin Z is safer showing better toxicity criteria and higher rat oral LD50 and rat chronic LOAEL (lowest observed adverse effect level). Chemometric analysis using principle component analysis (PCA) based on the binding energies observed for the compounds with respect to the three tested enzymes revealed the clustering of the compounds into different clusters. Eutypellazine M, scalusamide C, and gymnastatin Z appear in one cluster due to their closeness in activity. Thus, these compounds could serve as promising SARS-CoV-2 enzymes inhibitors that could help in alleviation of COVID-19 infection. Further investigations are recommended to confirm the results of molecular modelling.
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48
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Siswodihardjo S, Pratama MRF, Praditapuspa EN, Kesuma D, Poerwono H, Widiandani T. Boesenbergia Pandurata as an Anti-Breast Cancer Agent: Molecular Docking
and ADMET Study. LETT DRUG DES DISCOV 2022. [DOI: 10.2174/1570180819666211220111245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background:
Boesenbergia pandurata or fingerroot is known to have various pharmacological
activities, including anticancer properties. Extracts from these plants are known to inhibit the growth of
cancer cells, including breast cancer. Anti-breast cancer activity is significantly influenced by the inhibition
of two receptors: ER-α and HER2. However, it is unknown which metabolites of B. pandurata play
the most crucial role in exerting anticancer activity.
Objective:
This study aimed to determine the metabolites of B. pandurata with the best potential as ER-α
and HER2 inhibitors.
Method:
The method used was molecular docking of several B. pandurata metabolites to ER-α and
HER2 receptors, followed by an ADMET study of several metabolites with the best docking results.
Results:
The docking results showed eight metabolites with the best docking results for the two receptors
based on the docking score and ligand-receptor interactions. Of these eight compounds, compounds 11
((2S)-7,8-dihydro-5-hydroxy-2-methyl-2-(4''-methyl-3''-pentenyl)-8-phenyl-2H,6H-benzo(1,2-b-5,4-
b')dipyran-6-one) and 34 (geranyl-2,4-dihydroxy-6-phenethylbenzoate) showed the potential to inhibit
both receptors. Both ADMET profiles also showed mixed results; however, there is a possibility of further
development.
Conclusion:
In conclusion, the metabolites of B. pandurata, especially compounds 11 and 34, can be
developed as anti-breast cancer agents by inhibiting ER-α and HER2.
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Affiliation(s)
- Siswandono Siswodihardjo
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya
60115, Indonesia
| | - Mohammad Rizki Fadhil Pratama
- Doctoral Program of Pharmaceutical Science, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60115, Indonesia
- Department of Pharmacy, Faculty of Health Science, Universitas Muhammadiyah Palangkaraya, Palangka Raya
73111, Indonesia
| | - Ersanda Nurma Praditapuspa
- Master Program of Pharmaceutical Science, Faculty of Pharmacy, Universitas Airlangga, Surabaya
60115, Indonesia
| | - Dini Kesuma
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Surabaya, Surabaya
60293, Indonesia
| | - Hadi Poerwono
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya
60115, Indonesia
| | - Tri Widiandani
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya
60115, Indonesia
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Venugopal PP, Chakraborty D. Molecular mechanism of inhibition of COVID-19 main protease by β-adrenoceptor agonists and adenosine deaminase inhibitors using in silico methods. J Biomol Struct Dyn 2022; 40:5112-5127. [PMID: 33397209 PMCID: PMC7784836 DOI: 10.1080/07391102.2020.1868337] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Accepted: 12/17/2020] [Indexed: 11/07/2022]
Abstract
Novel coronavirus (COVID-19) responsible for viral pneumonia which emerged in late 2019 has badly affected the world. No clinically proven drugs are available yet as the targeted therapeutic agents for the treatment of this disease. The viral main protease which helps in replication and transcription inside the host can be an effective drug target. In the present study, we aimed to discover the potential of β-adrenoceptor agonists and adenosine deaminase inhibitors which are used in asthma and cancer/inflammatory disorders, respectively, as repurposing drugs against protease inhibitor by ligand-based and structure-based virtual screening using COVID-19 protease-N3 complex. The AARRR pharmacophore model was used to screen a set of 22,621 molecules to obtain hits, which were subjected to high-throughput virtual screening. Extra precision docking identified four top-scored molecules such as +/--fenoterol, FR236913 and FR230513 with lower binding energy from both categories. Docking identified three major hydrogen bonds with Gly143, Glu166 and Gln189 residues. 100 ns MD simulation was performed for four top-scored molecules to analyze the stability, molecular mechanism and energy requirements. MM/PBSA energy calculation suggested that van der Waals and electrostatic energy components are the main reasons for the stability of complexes. Water-mediated hydrogen bonds between protein-ligand and flexibility of the ligand are found to be responsible for providing extra stability to the complexes. The insights gained from this combinatorial approach can be used to design more potent and bio-available protease inhibitors against novel coronavirus.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Pushyaraga P. Venugopal
- Biophysical and Computational Chemistry Laboratory, Department of Chemistry, National Institute of Technology Karnataka, Mangalore, India
| | - Debashree Chakraborty
- Biophysical and Computational Chemistry Laboratory, Department of Chemistry, National Institute of Technology Karnataka, Mangalore, India
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50
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Chandra Manivannan A, Malaisamy A, Eswaran M, Meyyazhagan A, Arumugam VA, Rengasamy KRR, Balasubramanian B, Liu WC. Evaluation of Clove Phytochemicals as Potential Antiviral Drug Candidates Targeting SARS-CoV-2 Main Protease: Computational Docking, Molecular Dynamics Simulation, and Pharmacokinetic Profiling. Front Mol Biosci 2022; 9:918101. [PMID: 35836934 PMCID: PMC9273859 DOI: 10.3389/fmolb.2022.918101] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 05/19/2022] [Indexed: 01/16/2023] Open
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus can cause a sudden respiratory disease spreading with a high mortality rate arising with unknown mechanisms. Still, there is no proper treatment available to overcome the disease, which urges the research community and pharmaceutical industries to screen a novel therapeutic intervention to combat the current pandemic. This current study exploits the natural phytochemicals obtained from clove, a traditional natural therapeutic that comprises important bioactive compounds used for targeting the main protease of SARS-CoV-2. As a result, inhibition of viral replication effectively procures by targeting the main protease, which is responsible for the viral replication inside the host. Pharmacokinetic studies were evaluated for the property of drug likeliness. A total of 53 bioactives were subjected to the study, and four among them, namely, eugenie, syzyginin B, eugenol, and casuarictin, showed potential binding properties against the target SARS-CoV-2 main protease. The resultant best bioactive was compared with the commercially available standard drugs. Furthermore, validation of respective compounds with a comprehensive molecular dynamics simulation was performed using Schrödinger software. To further validate the bioactive phytochemicals and delimit the screening process of potential drugs against coronavirus disease 2019, in vitro and in vivo clinical studies are needed to prove their efficacy.
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Affiliation(s)
| | - Arunkumar Malaisamy
- Integrative Biology Division, International Centre for Genetic Engineering and Biotechnology, New Delhi, India
| | - Murugesh Eswaran
- Department of Bioinformatics, Bharathiar University, Coimbatore, India
| | - Arun Meyyazhagan
- Department of Life Sciences, CHRIST (Deemed to be University), Bengaluru, India
| | - Vijaya Anand Arumugam
- Department of Human Genetics and Molecular Biology, Bharathiar University, Coimbatore, India
| | - Kannan R. R. Rengasamy
- Department of Pharmacology, Centre for Transdisciplinary Research, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, India
| | | | - Wen-Chao Liu
- Department of Animal Science, College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang, China
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