Flavonol morin targets host ACE2, IMP-α, PARP-1 and viral proteins of SARS-CoV-2, SARS-CoV and MERS-CoV critical for infection and survival: a computational analysis

Abstract

A sudden outbreak of a novel coronavirus SARS-CoV-2 in 2019 has now emerged as a pandemic threatening to efface the existence of mankind. In absence of any valid and appropriate vaccines to combat this newly evolved agent, there is need of novel resource molecules for treatment and prophylaxis. To this effect, flavonol morin which is found in fruits, vegetables and various medicinal herbs has been evaluated for its antiviral potential in the present study. PASS analysis of morin versus reference antiviral drugs baricitinib, remdesivir and hydroxychloroquine revealed that morin displayed no violations of Lipinski’s rule of five and other druglikeness filters. Morin also displayed no tumorigenic, reproductive or irritant effects and exhibited good absorption and permeation through GI (clogP <5). In principal component analysis, morin appeared closest to baricitinib in 3D space. Morin displayed potent binding to spike glycoprotein, main protease 3CLPro and papain-like protease PLPro of SARS-CoV-2, SARS-CoV and MERS-CoV using molecular docking and significant binding to three viral-specific host proteins viz. human ACE2, importin-α and poly (ADP-ribose) polymerase (PARP)-1, further lending support to its antiviral efficacy. Additionally, morin displayed potent binding to pro-inflammatory cytokines IL-6, 8 and 10 also supporting its anti-inflammatory activity. MD simulation of morin with SARS-CoV-2 3CLPro and PLPro displayed strong stability at 300 K. Both complexes exhibited constant RMSDs of protein side chains and Cα atoms throughout the simulation run time. In conclusion, morin might hold considerable therapeutic potential for the treatment and management of not only COVID-19, but also SARS and MERS if studied further.

Communicated by Ramaswamy H. Sarma

Graphical Abstract

Keywords:

• SARS-CoV-2
• COVID-19
• MERS
• SARS
• coronaviruses
• flavonols
• morin
• molecular docking

Acknowledgements

The authors gratefully acknowledge Dr. Meraj Ahmad, Professor, Dept. of Sociology, University of Lucknow, Lucknow, India, for being the inspiration and motivation behind the present work in view of his exceptional work and contribution in the area of social sciences, social work, humanities and public health.

Author contributions

Author contributionsRA planned, conceptualized and supervised the study whereas AG, RA, SS, AS and AT carried out the computational analyses viz. molecular docking, molecular chemoinformatics and molecular dynamics simulations. RA performed calculations, data analysis and interpretation as well as drafted, edited and revised the manuscript. SS, KY, MAK, AKS and GKS edited, revised and critically reviewed the manuscript whereas BA co-ordinated the overall study design. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.