Preprint / Version 1

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

Authors

  • Shivananada Kandagalla Higher Medical & Biological School, Laboratory of Computational Modeling of Drugs, South Ural State University, Chelyabinsk, Chelyabinsk, Russia
  • Hrvoje Rimac Department of Medicinal Chemistry, University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia
  • Krishnamoorthy Gurushankar Higher Medical & Biological School, Laboratory of Computational Modeling of Drugs, South Ural State University, Chelyabinsk, Chelyabinsk, Russia
  • Jurica Novak Higher Medical & Biological School, Laboratory of Computational Modeling of Drugs, South Ural State University, Chelyabinsk, Chelyabinsk, Russia
  • Maria Grishina Higher Medical & Biological School, Laboratory of Computational Modeling of Drugs, South Ural State University, Chelyabinsk, Chelyabinsk, Russia
  • Vladimir Potemkin Higher Medical & Biological School, Laboratory of Computational Modeling of Drugs, South Ural State University, Chelyabinsk, Chelyabinsk, Russia

Keywords:

SARS-CoV-2, Indian ginseng, AlteQ, 3C-like proteinase, Complementarity principle, Withania somnifera

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

Author Biography

Krishnamoorthy Gurushankar, Higher Medical & Biological School, Laboratory of Computational Modeling of Drugs, South Ural State University, Chelyabinsk, Chelyabinsk, Russia

Department of Physics, Kalasalingam Academy of Research and Education, Krishnankoil, Tamilnadu, India

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