The Discovery of Small Allosteric and Active Site Inhibitors of the SARS-CoV-2 Main Protease via Structure-Based Virtual Screening and Biological Evaluation.

ABSTRACT: The main protease enzyme (M^pro) of SARS-CoV-2 is one of the most promising targets for COVID-19 treatment. Accordingly, in this work, a structure-based virtual screening of 3.8 million ligand libraries was carried out. After rigorous filtering, docking, and post screening assessments, 78 compounds were selected for biological evaluation, 3 of which showed promising inhibition of the M^pro enzyme. The obtained hits (CB03, GR04, and GR20) had reasonable potencies with K_i values in the medium to high micromolar range. Interestingly, while our most potent hit, GR20, was suggested to act via a reversible covalent mechanism, GR04 was confirmed as a noncompetitive inhibitor that seems to be one of a kind when compared to the other allosteric inhibitors discovered s

SUBMITTER: Mahgoub RE 

PROVIDER: S-EPMC9572942 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature