In-silico screening of plant-derived antivirals against main protease, 3CL^pro and endoribonuclease, NSP15 proteins of SARS-CoV-2

Abstract

Novel Coronavirus or SARS-CoV-2 outbreak has developed a pandemic condition all over the world. The virus is highly infectious and spreads by human to human local transmission mode. Till date, there is no vaccination or drugs been approved for the treatment by the World Health Organisation. Henceforth, the discovery of the potential drugs is an urgent and utmost requirement for the medical fraternity. Since, the side effects of plant-derived compounds will be lower compared to synthetic/chemical drugs. The Main protease (3CL^pro or NSP5) and endoribonuclease (NSP15) proteins are necessity for viral replication and its survival in the host cell. In the present study, in-silico approach of drug development was used to search for potential antiviral plant-derived compounds as inhibitors against SARS-CoV-2 replication proteins. Eight plant-derived compounds of which the antiviral activity was known and available, and two reported drugs against SARS-CoV-2 selected for the molecular docking analysis. The docking results suggested that bisdemethoxycurcumin, demethoxycurcumin, scutellarin, quercetin and myricetin showed least binding energy, i.e., greater than −6.5 Kcal/mol against 3CL^pro and endoribonuclease of SARS-CoV-2. Further studies of ADME-Tox and bioavailability of drugs were also performed that exhibited efficient parameters of drug likeness. Molecular dynamics simulation calculations were performed for the most negative binding affinity of the compound to evaluate the dynamic behavior,and stability of protein-ligand complex. Our findings suggest that these compounds could be potential inhibitors of SARS‐CoV-2 main protease and endoribonuclease. However, further in-vitro and pre-clinical experiments would validate the potential inhibitors of SARS‐CoV‐2 proteins.

Keywords:

• SARS-CoV-2
• COVID-19
• docking
• plant-derived compounds
• 3CL^pro
• endoribonuclease

Acknowledgements

The authors would like to thank Amity University Uttar Pradesh, India for providing facilities to carry out this work. The authors also would like to thank the researchers who generated and shared the sequencing and protein data of main protease (3CL^pro) and endoribonuclease (NSP15) proteins of SARS-CoV-2 in Protein Data Bank website (https://www.rcsb.org/). The authors would like to acknowledge Ms. Sapna Ratnakar, Ph.D. Scholar, School of Life Sciences, JNU for providing her support to carry out MDS. P.K. would like to thank DBT Project for supporting the research work and also thank Dr. Debabsisa Mohanty for providing the NII computational facility to carry out the simulation analysis.

Disclosure statement

The authors declare no potential conflicts of interest to disclose.

Authors contributions

All authors conceived, conducted and analyzed the results of experiment(s) equally. L.G. performed docking studies, manuscript editing; A.S. and S.G. drafted manuscript, performed ADMET studies; A.K.Y. manuscript editing, result analysis and P.K. performed molecular dynamics and simulations.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.