Potential inhibitors of SARS-CoV-2 (COVID 19) proteases PLpro and Mpro/ 3CLpro: molecular docking and simulation studies of three pertinent medicinal plant natural components

Devvret Verma; Debasis Mitra; Manish Paul; Priya Chaudhary; Anshul Kamboj; Hrudayanath Thatoi; Pracheta Janmeda; Divya Jain; Periyasamy Panneerselvam; Rakesh Shrivastav; Kumud Pant; Pradeep K Das Mohapatra

doi:10.1016/j.crphar.2021.100038

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

Curr Res Pharmacol Drug Discov. 2021:2:100038. doi: 10.1016/j.crphar.2021.100038. Epub 2021 Jun 5.

Authors

Affiliations

¹ Department of Biotechnology, Graphic Era (Deemed to be University), Dehradun, 248 002, Uttarakhand, India.
² Department of Microbiology, Raiganj University, Raiganj, 733 134, Uttar Dinajpur, West Bengal, India.
³ Department of Biotechnology, Maharaja Sriram Chandra Bhanja Deo University, Baripada, 757003, Odisha, India.
⁴ Department of Bioscience and Biotechnology, Banasthali University, Vanasthali, 304022, Rajasthan, India.
⁵ Microbiology, Crop Production Division, ICAR- National Rice Research Institute, Cuttack, 753 006, Odisha, India.
⁶ Department of Applied Sciences, NGF College of Engineering and Technology, Palwal, Haryana, India.
⁷ PAKB Environment Conservation Centre, Raiganj University, Raiganj, 733 134, Uttar Dinajpur, West Bengal, India.

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).