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

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.

Automated summary

Research has shown that withanolides from Ashwagandha have the potential to inhibit the activity of the cell surface receptor protein TMPRSS2 and the main viral protein Mpro that are crucial for COVID-19 virus entry into host cells and viral replication. This suggests that Ashwagandha may serve as a promising resource for the treatment of COVID-19.