Withasomniferol C, a new potential SARS-CoV-2 main protease inhibitor from the Withania somnifera plant proposed by in silico approaches

Shivananada Kandagalla; Hrvoje Rimac; Krishnamoorthy Gurushankar; Jurica Novak; Maria Grishina; Vladimir Potemkin

doi:10.7717/peerj.13374

Withasomniferol C, a new potential SARS-CoV-2 main protease inhibitor from the Withania somnifera plant proposed by in silico approaches

PeerJ. 2022 Jun 2:10:e13374. doi: 10.7717/peerj.13374. eCollection 2022.

Authors

Shivananada Kandagalla¹, Hrvoje Rimac², Krishnamoorthy Gurushankar^{1

3}, Jurica Novak¹, Maria Grishina¹, Vladimir Potemkin¹

Affiliations

¹ Higher Medical & Biological School, Laboratory of Computational Modeling of Drugs, South Ural State University, Chelyabinsk, Chelyabinsk, Russia.
² Department of Medicinal Chemistry, University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia.
³ Department of Physics, Kalasalingam Academy of Research and Education, Krishnankoil, Tamilnadu, India.

Abstract

Exploring potent herbal medicine candidates is a promising strategy for combating a pandemic in the present global health crisis. In Ayurveda (a traditional medicine system in India), Withania somnifera (WS) is one of the most important herbs and it has been used for millennia as Rasayana (a type of juice) for its wide-ranging health benefits. WS phytocompounds display a broad spectrum of biological activities (such as antioxidant, anticancer and antimicrobial) modulate detoxifying enzymes, and enhance immunity. Inspired by the numerous biological actions of WS phytocompounds, the present investigation explored the potential of the WS phytocompounds against the SARS-CoV-2 main protease (3CL^pro). We selected 11 specific withanolide compounds, such as withaphysalin, withasomniferol, and withafastuosin, through manual literature curation against 3CL^pro. A molecular similarity analysis showed their similarity with compounds that have an established inhibitory activity against the SARS-CoV-2. In silico molecular docking and molecular dynamics simulations elucidated withasomniferol C (WS11) as a potential candidate against SARS-CoV-2 3CL^pro. Additionally, the present work also presents a new method of validating docking poses using the AlteQ method.

Keywords: 3C-like proteinase; AlteQ; Complementarity principle; Indian ginseng; SARS-CoV-2; Withania somnifera.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Molecular Docking Simulation
SARS-CoV-2
Withania*

Substances

3C-like proteinase, SARS-CoV-2

Grants and funding

This study was funded by RFBR, DST, CNPq, SAMRC, project number 20-53-80002. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.