{"title":"索非布韦和瑞德西韦与RNA定向RNA聚合酶相互作用的计算见解:配体筛选,对接模拟和相互作用分析","authors":"Sirvan Abbasbeigi","doi":"10.1007/s00769-025-01652-y","DOIUrl":null,"url":null,"abstract":"<div><p>This review explores sofosbuvir, a nucleoside analog approved for hepatitis C, as a potential inhibitor of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), compared to remdesivir, which is constrained by hepatic and renal toxicity. RdRp, essential for viral replication, is a key target for COVID-19 therapeutics. Ligand-based virtual screening through the DrugRep virtual screening server, utilizing algorithms like Morgan fingerprint, identified compounds structurally akin to remdesivir. Structure-based molecular docking with CB-Dock2 and AutoDock Vina targeted the RdRp structure (PDB ID: 7BV2), revealing sofosbuvir’s binding affinity of − 7.6 kcal/mol, slightly lower than remdesivir’s − 8.4 kcal/mol, but with strong hydrogen bonds to ARG349 (3.05, 2.99, 2.89 Å) and CYS395 (3.41 Å), alongside Pi-Sigma and Pi-Alkyl interactions with PRO461 and VAL315. Molecular dynamics simulations (30 ns, LAMMPS) suggest sofosbuvir’s stability, with lower RMSD (~ 1.4 Å vs. ~ 1.8 Å for remdesivir) and more persistent hydrogen bonds, supported by its reliable structure and connectivity. Compared to remdesivir, sofosbuvir exhibits fewer unfavorable interactions and a well-established safety profile. Interaction analyses using BIOVIA Discovery Studio and LigPlot + confirmed sofosbuvir’s stability within the RdRp active site, corroborated by in vitro and clinical evidence. These findings highlight the pivotal role of in silico methods in drug repurposing for COVID-19. However, experimental validation is crucial to confirm sofosbuvir’s efficacy, particularly against SARS-CoV-2 variants, and to explore its therapeutic potential for addressing current and future viral threats.</p></div>","PeriodicalId":454,"journal":{"name":"Accreditation and Quality Assurance","volume":"30 5","pages":"493 - 505"},"PeriodicalIF":1.0000,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Computational insights into the interactions of sofosbuvir and remdesivir with RNA-directed RNA polymerase: ligand screening, docking simulations, and interaction analysis\",\"authors\":\"Sirvan Abbasbeigi\",\"doi\":\"10.1007/s00769-025-01652-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>This review explores sofosbuvir, a nucleoside analog approved for hepatitis C, as a potential inhibitor of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), compared to remdesivir, which is constrained by hepatic and renal toxicity. RdRp, essential for viral replication, is a key target for COVID-19 therapeutics. Ligand-based virtual screening through the DrugRep virtual screening server, utilizing algorithms like Morgan fingerprint, identified compounds structurally akin to remdesivir. Structure-based molecular docking with CB-Dock2 and AutoDock Vina targeted the RdRp structure (PDB ID: 7BV2), revealing sofosbuvir’s binding affinity of − 7.6 kcal/mol, slightly lower than remdesivir’s − 8.4 kcal/mol, but with strong hydrogen bonds to ARG349 (3.05, 2.99, 2.89 Å) and CYS395 (3.41 Å), alongside Pi-Sigma and Pi-Alkyl interactions with PRO461 and VAL315. Molecular dynamics simulations (30 ns, LAMMPS) suggest sofosbuvir’s stability, with lower RMSD (~ 1.4 Å vs. ~ 1.8 Å for remdesivir) and more persistent hydrogen bonds, supported by its reliable structure and connectivity. Compared to remdesivir, sofosbuvir exhibits fewer unfavorable interactions and a well-established safety profile. Interaction analyses using BIOVIA Discovery Studio and LigPlot + confirmed sofosbuvir’s stability within the RdRp active site, corroborated by in vitro and clinical evidence. These findings highlight the pivotal role of in silico methods in drug repurposing for COVID-19. However, experimental validation is crucial to confirm sofosbuvir’s efficacy, particularly against SARS-CoV-2 variants, and to explore its therapeutic potential for addressing current and future viral threats.</p></div>\",\"PeriodicalId\":454,\"journal\":{\"name\":\"Accreditation and Quality Assurance\",\"volume\":\"30 5\",\"pages\":\"493 - 505\"},\"PeriodicalIF\":1.0000,\"publicationDate\":\"2025-07-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Accreditation and Quality Assurance\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s00769-025-01652-y\",\"RegionNum\":4,\"RegionCategory\":\"工程技术\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"CHEMISTRY, ANALYTICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Accreditation and Quality Assurance","FirstCategoryId":"5","ListUrlMain":"https://link.springer.com/article/10.1007/s00769-025-01652-y","RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CHEMISTRY, ANALYTICAL","Score":null,"Total":0}
Computational insights into the interactions of sofosbuvir and remdesivir with RNA-directed RNA polymerase: ligand screening, docking simulations, and interaction analysis
This review explores sofosbuvir, a nucleoside analog approved for hepatitis C, as a potential inhibitor of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), compared to remdesivir, which is constrained by hepatic and renal toxicity. RdRp, essential for viral replication, is a key target for COVID-19 therapeutics. Ligand-based virtual screening through the DrugRep virtual screening server, utilizing algorithms like Morgan fingerprint, identified compounds structurally akin to remdesivir. Structure-based molecular docking with CB-Dock2 and AutoDock Vina targeted the RdRp structure (PDB ID: 7BV2), revealing sofosbuvir’s binding affinity of − 7.6 kcal/mol, slightly lower than remdesivir’s − 8.4 kcal/mol, but with strong hydrogen bonds to ARG349 (3.05, 2.99, 2.89 Å) and CYS395 (3.41 Å), alongside Pi-Sigma and Pi-Alkyl interactions with PRO461 and VAL315. Molecular dynamics simulations (30 ns, LAMMPS) suggest sofosbuvir’s stability, with lower RMSD (~ 1.4 Å vs. ~ 1.8 Å for remdesivir) and more persistent hydrogen bonds, supported by its reliable structure and connectivity. Compared to remdesivir, sofosbuvir exhibits fewer unfavorable interactions and a well-established safety profile. Interaction analyses using BIOVIA Discovery Studio and LigPlot + confirmed sofosbuvir’s stability within the RdRp active site, corroborated by in vitro and clinical evidence. These findings highlight the pivotal role of in silico methods in drug repurposing for COVID-19. However, experimental validation is crucial to confirm sofosbuvir’s efficacy, particularly against SARS-CoV-2 variants, and to explore its therapeutic potential for addressing current and future viral threats.
期刊介绍:
Accreditation and Quality Assurance has established itself as the leading information and discussion forum for all aspects relevant to quality, transparency and reliability of measurement results in chemical and biological sciences. The journal serves the information needs of researchers, practitioners and decision makers dealing with quality assurance and quality management, including the development and application of metrological principles and concepts such as traceability or measurement uncertainty in the following fields: environment, nutrition, consumer protection, geology, metallurgy, pharmacy, forensics, clinical chemistry and laboratory medicine, and microbiology.