Structure-Based Design and Molecular Simulations of Some Quercetin-Based Drugs as Repurposable Inhibitors of SARS-CoV-2 Main Protease

In this study, virtual screening and molecular dynamics (MD) protocols were applied to screen 2826 FDA-approved natural product drugs from the Selleckchem.com library for prospective inhibitors of SARS-CoV-2 main protease. From through HTVS, SP XP docking analysis, hyperoside, rutin hydrate, rutoside quercitrin displayed a stronger binding affinity with respective scores –11.389, –11.340, –11.087 –10.232 kcal/mol than co-crystallized N-[2-(5-fluoro-1H-indol-3-yl)ethyl]acetamide (HWH) positive inhibitors, lopinavir ritonavir which scored –5.493, –6.463 –6.221 respectively. Selectively, free energy, MMGB(SA) hyperoside hydrate was observed as –21.55 –25.82 respectively compared –17.66 –5.28 Consistently, selected good thermodynamics conformational stability, thus, recommended promising repurposable protease amenable further studies. HIGHLIGHTS Main represents plausible target mitigating viral replication Natural are safer cheaper combating COVID-19 Hyperoside, strong stability They studies GRAPHICAL ABSTRACT