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

Author:

Kandagalla Shivananada1,Rimac Hrvoje2,Gurushankar Krishnamoorthy13,Novak Jurica1,Grishina Maria1,Potemkin Vladimir1

Affiliation:

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 (3CLpro). We selected 11 specific withanolide compounds, such as withaphysalin, withasomniferol, and withafastuosin, through manual literature curation against 3CLpro. 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 3CLpro. Additionally, the present work also presents a new method of validating docking poses using the AlteQ method.

Funder

RFBR, DST, CNPq, SAMRC

Publisher

PeerJ

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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3. Withanone from withania somnif-era attenuates sars-cov-2 rbd and host ace2 interactions to rescue spike protein induced pathologies in humanized zebrafish model;Balkrishna;Drug Design, Development and Therapy,2021

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