Microsecond MD Simulation and Multiple-Conformation Virtual Screening to Identify Potential Anti-COVID-19 Inhibitors Against SARS-CoV-2 Main Protease

作者: Evzen Boura , Vikash Kumar Dubey , Poonam Singh , Sanjeev Kumar Singh , Umesh Panwar

DOI: 10.3389/FCHEM.2020.595273

关键词: Oxyanion holeProteaseComputational biologyActive siteVirtual screeningDocking (molecular)EnzymeChemistryAmino acidMolecular model

摘要: The recent pandemic outbreak of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raised global health and economic concerns. Phylogenetically, SARS-CoV-2 is closely related to SARS-CoV, both encode the enzyme main protease (Mpro/3CLpro), which can be a potential target inhibiting viral replication. Through this work, we have compiled structural aspects Mpro conformational changes, with molecular modeling 1-μs MD simulations. Long-scale simulation resolves mechanism role crucial amino acids involved in protein stability, followed ensemble docking provides compounds from Traditional Chinese Medicine (TCM) database. These lead directly interact active site residues (His41, Gly143, Cys145) Mpro, plays enzymatic activity. binding mode analysis S1, S1', S2, S4 subsites, screened may functional for distortion oxyanion hole reaction mechanism, it inhibition SARS-CoV-2. hit are naturally occurring compounds; they provide sustainable readily available option medical treatment humans infected Henceforth, extensive through approaches explained that proposed molecules might promising inhibitors subjected experimental validation.

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