Molecular mechanism of anti-SARS-CoV2 activity of Ashwagandha-derived withanolides

Int J Biol Macromol. 2021 Aug 1:184:297-312. doi: 10.1016/j.ijbiomac.2021.06.015. Epub 2021 Jun 9.

Abstract

COVID-19 caused by SARS-CoV-2 corona virus has become a global pandemic. In the absence of drugs and vaccine, and premises of time, efforts and cost required for their development, natural resources such as herbs are anticipated to provide some help and may also offer a promising resource for drug development. Here, we have investigated the therapeutic prospective of Ashwagandha for the COVID-19 pandemic. Nine withanolides were tested in silico for their potential to target and inhibit (i) cell surface receptor protein (TMPRSS2) that is required for entry of virus to host cells and (ii) viral protein (the main protease Mpro) that is essential for virus replication. We report that the withanolides possess capacity to inhibit the activity of TMPRSS2 and Mpro. Furthermore, withanolide-treated cells showed downregulation of TMPRSS2 expression and inhibition of SARS-CoV-2 replication in vitro, suggesting that Ashwagandha may provide a useful resource for COVID-19 treatment.

Keywords: COVID-19; Main protease (M(pro)); SARS-CoV-2; Transmembrane protease serine 2 (TMPRSS2); Withanolides; Withanosides.

MeSH terms

  • A549 Cells
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Computer Simulation
  • Down-Regulation
  • Gene Expression Regulation / drug effects
  • Humans
  • MCF-7 Cells
  • Models, Molecular
  • Molecular Dynamics Simulation
  • Plant Extracts / chemistry*
  • Protein Conformation
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / physiology*
  • Serine Endopeptidases / chemistry
  • Serine Endopeptidases / metabolism*
  • Viral Matrix Proteins / chemistry
  • Viral Matrix Proteins / metabolism*
  • Virus Internalization / drug effects
  • Withanolides / chemistry
  • Withanolides / pharmacology*

Substances

  • Antiviral Agents
  • Plant Extracts
  • Viral Matrix Proteins
  • Withanolides
  • membrane protein, SARS-CoV-2
  • Serine Endopeptidases
  • TMPRSS2 protein, human
  • Ashwagandha