Curr Res Pharmacol Drug Discov . Potential inhibitors of SARS-CoV-2 (COVID 19) proteases PL pro and M pro/ 3CL pro: molecular docking and simulation studies of three pertinent medicinal plant natural components

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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 ^pro and M ^pro/ 3CL ^pro: molecular docking and simulation studies of three pertinent medicinal plant natural components


Devvret Verma ¹ , Debasis Mitra ² , Manish Paul ³ , Priya Chaudhary ⁴ , Anshul Kamboj ¹ , Hrudayanath Thatoi ³ , Pracheta Janmeda ⁴ , Divya Jain ⁴ , Periyasamy Panneerselvam ⁵ , Rakesh Shrivastav ⁶ , Kumud Pant ¹ , Pradeep K Das Mohapatra ^{2 7}



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^pro) and main protease (M^pro)/3-chymotrypsin-like protease (3CL^pro). 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^pro and M^pro/3CL^pro 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).