Computational Identification of Possible Allosteric Sites and Modulators of the SARS-CoV-2 Main Protease.

ABSTRACT: In this study, we target the main protease (M^pro) of the SARS-CoV-2 virus as it is a crucial enzyme for viral replication. Herein, we report three plausible allosteric sites on M^pro that can expand structure-based drug discovery efforts for new M^pro inhibitors. To find these sites, we used mixed-solvent molecular dynamics (MixMD) simulations, an efficient computational protocol that finds binding hotspots through mapping the surface of unbound proteins with 5% cosolvents in water. We have used normal mode analysis to support our claim of allosteric control for these sites. Further, we have performed virtual screening against the sites with 361 hits from M^pro screenings available through the National Center for Advancing Translational Sciences (NC

SUBMITTER: DasGupta D 

PROVIDER: S-EPMC10262278 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature