Shilu M. Mathew, F. Benslimane, A. Althani, H. Yassine
{"title":"新型SARS-Cov-2刺突受体结合域潜在抑制的抗病毒药物和天然化合物的虚拟筛选","authors":"Shilu M. Mathew, F. Benslimane, A. Althani, H. Yassine","doi":"10.29117/quarfe.2020.0281","DOIUrl":null,"url":null,"abstract":"Background: The spike (S) protein of SARS-CoV-2 harbors the receptor-binding domain (RBD) that mediates the virus's entry to host cells. The aim of this study was to identify novel inhibitors that target the RBD domain of S-protein through computational screening of chemical and natural compounds. Method: The S protein was modelled from the recently resolved and the previously described SARS-CoV protein structures. CLC Drug Discovery was used to computationally screen for potential inhibitory effects of currently prescribed drugs (n= 22) anti-viral natural drugs (n=100), natural compounds (n= 35032). QSAR was also performed. Results: Among currently precribed drugs to treat SARS-CoV2, hydroxychloroquine and favipiravir were identified as the best binders with an average of 4Hbonds, the binding affinity (BA): -36.66 kcal·mol−1, and interaction energy (IE): -6.63 kcal·mol−1. After the evaluation of anti-viral compounds, fosamprenavir and abacavir showed effective binding of 5H-bonds, with average BA: -18.75 kcal·mol−1, and IE: -3.57 kcal·mol−1. Furthermore, screening of 100 natural anti-viral compounds predicted potential binding modes of glycyrrhizin, nepritin, punicalagin, EGCG, and theaflavin (average BA: -49.88 kcal·mol−1, and IE: -4.35 kcal·mol−1). Additionally, the study reports 25 natural compounds that showed effective binding with an improved average BA: 51.46 kcal·mol−1. Conclusion: Using computational screening, we identified potential SARSCoV-2 spike inhibitors that bind to the RBD region.","PeriodicalId":169505,"journal":{"name":"University of the Future: Re-Imagining Research and Higher Education","volume":"82 1","pages":"0"},"PeriodicalIF":0.0000,"publicationDate":"2020-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Virtual Screening of Anti-Viral Drugs and Natural Compounds for Potential Inhibition of the Novel SARS-Cov-2 Spike Receptor-Binding Domain\",\"authors\":\"Shilu M. Mathew, F. Benslimane, A. Althani, H. Yassine\",\"doi\":\"10.29117/quarfe.2020.0281\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background: The spike (S) protein of SARS-CoV-2 harbors the receptor-binding domain (RBD) that mediates the virus's entry to host cells. The aim of this study was to identify novel inhibitors that target the RBD domain of S-protein through computational screening of chemical and natural compounds. Method: The S protein was modelled from the recently resolved and the previously described SARS-CoV protein structures. CLC Drug Discovery was used to computationally screen for potential inhibitory effects of currently prescribed drugs (n= 22) anti-viral natural drugs (n=100), natural compounds (n= 35032). QSAR was also performed. Results: Among currently precribed drugs to treat SARS-CoV2, hydroxychloroquine and favipiravir were identified as the best binders with an average of 4Hbonds, the binding affinity (BA): -36.66 kcal·mol−1, and interaction energy (IE): -6.63 kcal·mol−1. After the evaluation of anti-viral compounds, fosamprenavir and abacavir showed effective binding of 5H-bonds, with average BA: -18.75 kcal·mol−1, and IE: -3.57 kcal·mol−1. Furthermore, screening of 100 natural anti-viral compounds predicted potential binding modes of glycyrrhizin, nepritin, punicalagin, EGCG, and theaflavin (average BA: -49.88 kcal·mol−1, and IE: -4.35 kcal·mol−1). Additionally, the study reports 25 natural compounds that showed effective binding with an improved average BA: 51.46 kcal·mol−1. Conclusion: Using computational screening, we identified potential SARSCoV-2 spike inhibitors that bind to the RBD region.\",\"PeriodicalId\":169505,\"journal\":{\"name\":\"University of the Future: Re-Imagining Research and Higher Education\",\"volume\":\"82 1\",\"pages\":\"0\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2020-10-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"University of the Future: Re-Imagining Research and Higher Education\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.29117/quarfe.2020.0281\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"University of the Future: Re-Imagining Research and Higher Education","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.29117/quarfe.2020.0281","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Virtual Screening of Anti-Viral Drugs and Natural Compounds for Potential Inhibition of the Novel SARS-Cov-2 Spike Receptor-Binding Domain
Background: The spike (S) protein of SARS-CoV-2 harbors the receptor-binding domain (RBD) that mediates the virus's entry to host cells. The aim of this study was to identify novel inhibitors that target the RBD domain of S-protein through computational screening of chemical and natural compounds. Method: The S protein was modelled from the recently resolved and the previously described SARS-CoV protein structures. CLC Drug Discovery was used to computationally screen for potential inhibitory effects of currently prescribed drugs (n= 22) anti-viral natural drugs (n=100), natural compounds (n= 35032). QSAR was also performed. Results: Among currently precribed drugs to treat SARS-CoV2, hydroxychloroquine and favipiravir were identified as the best binders with an average of 4Hbonds, the binding affinity (BA): -36.66 kcal·mol−1, and interaction energy (IE): -6.63 kcal·mol−1. After the evaluation of anti-viral compounds, fosamprenavir and abacavir showed effective binding of 5H-bonds, with average BA: -18.75 kcal·mol−1, and IE: -3.57 kcal·mol−1. Furthermore, screening of 100 natural anti-viral compounds predicted potential binding modes of glycyrrhizin, nepritin, punicalagin, EGCG, and theaflavin (average BA: -49.88 kcal·mol−1, and IE: -4.35 kcal·mol−1). Additionally, the study reports 25 natural compounds that showed effective binding with an improved average BA: 51.46 kcal·mol−1. Conclusion: Using computational screening, we identified potential SARSCoV-2 spike inhibitors that bind to the RBD region.