Screening of plant-based natural compounds as a potential COVID-19 main protease inhibitor: an in silico docking and molecular dynamics simulation approach

Abstract

A new strain of coronavirus (CoV) has been identified as SARS-CoV-2, which is responsible for the recent COVID-19 pandemic. Currently, there is no approved vaccine or drug available to combat the pandemic. COVID-19 main protease (M^pro) is a key CoV enzyme, which plays an important role in triggering viral replication and transcription, turns it into an attractive target. Therefore, we aim to screen natural products library to find out potential COVID-19 M^pro inhibitors. Plant-based natural compounds from Sigma-Aldrich plant profiler chemical library have been screened through virtual molecular docking and molecular dynamics simulation to identify potential inhibitors of COVID M^pro. Our virtual molecular docking results have shown that there are twenty-eight natural compounds with a greater binding affinity toward the COVID-19 M^pro inhibition site as compared to the co-crystal native ligand Inhibitor N3 (-7.9 kcal/mol). Also, molecular dynamics simulation results have confirmed that Peonidin 3-O-glucoside, Kaempferol 3-O-β–rutinoside, 4-(3,4-Dihydroxyphenyl)-7-methoxy-5-[(6-O-β-D-xylopyranosyl-β-D-glucopyranosyl)oxy]-2H-1-benzopyran-2-one, Quercetin-3-D-xyloside, and Quercetin 3-O-α-L-arabinopyranoside (selected based on the docking score) possess a significant amount of dynamic properties such as stability, flexibility and binding energy. Our In silco results suggests that all the above mention natural compounds have the potential to be developed as a COVID-19 M^pro inhibitor. But before that, it must go through under the proper preclinical and clinical trials for further scientific validation.

Communicated by Ramaswamy H. Sarma

Keywords:

• Coronavirus (SARS-CoV-2)
• COVID-19 main protease (Mpro)
• natural compounds
• in silico molecular docking (Autodock vina)
• molecular dynamics (MD) simulation (Gromacs)

Acknowledgements

We would like to acknowledge the Indian Institute of Technology Kharagpur, India, Indian Council of Medical Research, Council of Scientific and Industrial Research, and J C Bose Fellowship (SERB, India) for providing structural and financial support.

Disclosure statement

No potential conflict of interest was reported by the authors.