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

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Sci Rep


. 2021 Oct 13;11(1):20295.
doi: 10.1038/s41598-021-99165-4.
Identification of antiviral phytochemicals as a potential SARS-CoV-2 main protease (M ^pro) inhibitor using docking and molecular dynamics simulations


Chirag N Patel ¹ , Siddhi P Jani ¹ , Dharmesh G Jaiswal ¹ , Sivakumar Prasanth Kumar ¹ , Naman Mangukia ^{1 2} , Robin M Parmar ³ , Rakesh M Rawal ⁴ , Himanshu A Pandya ⁵



Affiliations

• PMID: 34645849
• DOI: 10.1038/s41598-021-99165-4

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.