A higher flexibility at the SARS-CoV-2 main protease active site compared to SARS-CoV and its potentialities for new inhibitor virtual screening targeting multi-conformers.

ABSTRACT: The main-protease (M^pro) catalyzes a crucial step for the SARS-CoV-2 life cycle. The recent SARS-CoV-2 presents the main protease (M^CoV2_pro) with 12 mutations compared to SARS-CoV (M^CoV1_pro). Recent studies point out that these subtle differences lead to mobility variances at the active site loops with functional implications. We use metadynamics simulations and a sort of computational analysis to probe the dynamic, pharmacophoric and catalytic environment differences between the monomers of both enzymes. So, we verify how much intrinsic distinctions are preserved in the functional dimer of M^CoV2_pro, as well as its implications for ligand accessibility and optimized drug screening. We find a significantly higher a

SUBMITTER: Rocha REO 

PROVIDER: S-EPMC8127201 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature