tetano
Editor, Senior Moderator
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 [SUP]pro[/SUP]) inhibitor using docking and molecular dynamics simulations
Chirag N Patel[SUP] 1 [/SUP], Siddhi P Jani[SUP] 1 [/SUP], Dharmesh G Jaiswal[SUP] 1 [/SUP], Sivakumar Prasanth Kumar[SUP] 1 [/SUP], Naman Mangukia[SUP] 1 2 [/SUP], Robin M Parmar[SUP] 3 [/SUP], Rakesh M Rawal[SUP] 4 [/SUP], Himanshu A Pandya[SUP] 5 [/SUP]
Affiliations
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[SUP]pro[/SUP]) 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[SUP]pro[/SUP] 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[SUP]pro[/SUP] 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[SUP]pro[/SUP] inhibitors.
. 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 [SUP]pro[/SUP]) inhibitor using docking and molecular dynamics simulations
Chirag N Patel[SUP] 1 [/SUP], Siddhi P Jani[SUP] 1 [/SUP], Dharmesh G Jaiswal[SUP] 1 [/SUP], Sivakumar Prasanth Kumar[SUP] 1 [/SUP], Naman Mangukia[SUP] 1 2 [/SUP], Robin M Parmar[SUP] 3 [/SUP], Rakesh M Rawal[SUP] 4 [/SUP], Himanshu A Pandya[SUP] 5 [/SUP]
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[SUP]pro[/SUP]) 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[SUP]pro[/SUP] 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[SUP]pro[/SUP] 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[SUP]pro[/SUP] inhibitors.