tetano
Editor, Senior Moderator
Curr Res Pharmacol Drug Discov
. 2021;2:100038.
doi: 10.1016/j.crphar.2021.100038. Epub 2021 Jun 5.
Potential inhibitors of SARS-CoV-2 (COVID 19) proteases PL [SUP]pro[/SUP] and M [SUP]pro[/SUP]/ 3CL [SUP]pro[/SUP]: molecular docking and simulation studies of three pertinent medicinal plant natural components
Devvret Verma[SUP] 1 [/SUP], Debasis Mitra[SUP] 2 [/SUP], Manish Paul[SUP] 3 [/SUP], Priya Chaudhary[SUP] 4 [/SUP], Anshul Kamboj[SUP] 1 [/SUP], Hrudayanath Thatoi[SUP] 3 [/SUP], Pracheta Janmeda[SUP] 4 [/SUP], Divya Jain[SUP] 4 [/SUP], Periyasamy Panneerselvam[SUP] 5 [/SUP], Rakesh Shrivastav[SUP] 6 [/SUP], Kumud Pant[SUP] 1 [/SUP], Pradeep K Das Mohapatra[SUP] 2 7 [/SUP]
Affiliations
Abstract
The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - coronavirus disease 2019 (COVID-19) has raised a severe global public health issue and creates a pandemic situation. The present work aims to study the molecular -docking and dynamic of three pertinent medicinal plants i.e. Eurycoma harmandiana, Sophora flavescens and Andrographis paniculata phyto-compounds against SARS-COV-2 papain-like protease (PL[SUP]pro[/SUP]) and main protease (M[SUP]pro[/SUP])/3-chymotrypsin-like protease (3CL[SUP]pro[/SUP]). The interaction of protein targets and ligands was performed through AutoDock-Vina visualized using PyMOL and BIOVIA-Discovery Studio 2020. Molecular docking with canthin-6-one 9-O-beta-glucopyranoside showed highest binding affinity and less binding energy with both PL[SUP]pro[/SUP] and M[SUP]pro[/SUP]/3CL[SUP]pro[/SUP] proteases and was subjected to molecular dynamic (MD) simulations for a period of 100ns. Stability of the protein-ligand complexes was evaluated by different analyses. The binding free energy calculated using MM-PBSA and the results showed that the molecule must have stable interactions with the protein binding site. ADMET analysis of the compounds suggested that it is having drug-like properties like high gastrointestinal (GI) absorption, no blood-brain barrier permeability and high lipophilicity. The outcome revealed that canthin-6-one 9-O-beta-glucopyranoside can be used as a potential natural drug against COVID-19 protease.
Keywords: Canthin-6-one 9-O-Beta-glucopyranoside; Molecular dynamics; Natural inhibitor; PLpro-Mpro/3CLpro; SARS-CoV-2 (COVID-19).
. 2021;2:100038.
doi: 10.1016/j.crphar.2021.100038. Epub 2021 Jun 5.
Potential inhibitors of SARS-CoV-2 (COVID 19) proteases PL [SUP]pro[/SUP] and M [SUP]pro[/SUP]/ 3CL [SUP]pro[/SUP]: molecular docking and simulation studies of three pertinent medicinal plant natural components
Devvret Verma[SUP] 1 [/SUP], Debasis Mitra[SUP] 2 [/SUP], Manish Paul[SUP] 3 [/SUP], Priya Chaudhary[SUP] 4 [/SUP], Anshul Kamboj[SUP] 1 [/SUP], Hrudayanath Thatoi[SUP] 3 [/SUP], Pracheta Janmeda[SUP] 4 [/SUP], Divya Jain[SUP] 4 [/SUP], Periyasamy Panneerselvam[SUP] 5 [/SUP], Rakesh Shrivastav[SUP] 6 [/SUP], Kumud Pant[SUP] 1 [/SUP], Pradeep K Das Mohapatra[SUP] 2 7 [/SUP]
Affiliations
- PMID: 34870149
- PMCID: PMC8178537
- DOI: 10.1016/j.crphar.2021.100038
Abstract
The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - coronavirus disease 2019 (COVID-19) has raised a severe global public health issue and creates a pandemic situation. The present work aims to study the molecular -docking and dynamic of three pertinent medicinal plants i.e. Eurycoma harmandiana, Sophora flavescens and Andrographis paniculata phyto-compounds against SARS-COV-2 papain-like protease (PL[SUP]pro[/SUP]) and main protease (M[SUP]pro[/SUP])/3-chymotrypsin-like protease (3CL[SUP]pro[/SUP]). The interaction of protein targets and ligands was performed through AutoDock-Vina visualized using PyMOL and BIOVIA-Discovery Studio 2020. Molecular docking with canthin-6-one 9-O-beta-glucopyranoside showed highest binding affinity and less binding energy with both PL[SUP]pro[/SUP] and M[SUP]pro[/SUP]/3CL[SUP]pro[/SUP] proteases and was subjected to molecular dynamic (MD) simulations for a period of 100ns. Stability of the protein-ligand complexes was evaluated by different analyses. The binding free energy calculated using MM-PBSA and the results showed that the molecule must have stable interactions with the protein binding site. ADMET analysis of the compounds suggested that it is having drug-like properties like high gastrointestinal (GI) absorption, no blood-brain barrier permeability and high lipophilicity. The outcome revealed that canthin-6-one 9-O-beta-glucopyranoside can be used as a potential natural drug against COVID-19 protease.
Keywords: Canthin-6-one 9-O-Beta-glucopyranoside; Molecular dynamics; Natural inhibitor; PLpro-Mpro/3CLpro; SARS-CoV-2 (COVID-19).