Identification of antiviral phytochemicals as a potential SARS-CoV-2 main protease (M^pro) inhibitor using docking and molecular dynamics simulations.

ABSTRACT: Novel SARS-CoV-2, an etiological factor of Coronavirus disease 2019 (COVID-19), poses a great challenge to the public health care system. Among other druggable targets of SARS-Cov-2, the main protease (M^pro) is regarded as a prominent enzyme target for drug developments owing to its crucial role in virus replication and transcription. We pursued a computational investigation to identify M^pro inhibitors from a compiled library of natural compounds with proven antiviral activities using a hierarchical workflow of molecular docking, ADMET assessment, dynamic simulations and binding free-energy calculations. Five natural compounds, Withanosides V and VI, Racemosides A and B, and Shatavarin IX, obtained better binding affinity and attained stable interactions with M^pro key pocket residues. These intermolecular key interactions were also retained profoundly in the simulation trajectory of 100 ns time scale indicating tight receptor binding. Free energy calculations prioritized Withanosides V and VI as the top candidates that can act as effective SARS-CoV-2 M^pro inhibitors.

SUBMITTER: Patel CN 

PROVIDER: S-EPMC8514552 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature