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

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 M pro ) that is essential for virus replication. We report that the withanolides possess capacity to inhibit the activity of TMPRSS2 and M pro . 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.

Comparative computational and experimental analyses of some natural small molecules to restore transcriptional activation function of p53 in cancer cells harbouring wild type and p53Ser46 mutant

“…We next examined the effect of selected compounds on p53 activity in vitro using U2OS cells (possessing wild type p53) and HSC3 cells (possessing p53 Ser46mutant ). IC50 concentrations of each of the compounds were determined by cell viability assays and were consistent with the earlier reports ( Dhanjal et al., 2021 ; Garg et al., 2020 ; A. Kaul et al., 2021 ; Kumar et al., 2022 ).…”

Critical factors influencing in vitro propagation and modulation of important secondary metabolites in Withania somnifera (L.) dunal

“…Among medicinal plants, Withania somnifera occupies a distinct position owing to its immense medicinal properties including anti-cancer, cardioprotective, anti-inflammatory, immunomodulatory, anti-coagulant, anti-diabetic, anti-oxidant, and neuroprotective (Kaur et al 2021a ; Sangwan and Sangwan 2014 ). In silico studies on W. somnifera revealed its potential against COVID-19 by inhibiting the cell surface receptor protein (TMPRSS2) and viral protein (M pro ) of SARS-CoV-2 (Dhanjal et al 2021 ). The potent therapeutic potential of this plant is mainly due to the existence of different bioactive compounds including alkaloids, steroidal lactones, glycowithanolides, sterols, flavonoids, and phenolics (Chaurasiya et al 2012 ).…”

Potential of Withaferin-A, Withanone and Caffeic Acid Phenethyl ester as ATP-competitive inhibitors of BRAF: A bioinformatics study

“…The approximation and parameterization of atomic-level forces are the main limitations of the different force fields, which may further lead to variations in the ensemble generated by the simulation ( Wang and O'Mara, 2021 ). In the current study, different force field effects have not been investigated on the studied systems, but only a well-known force field for protein and small molecules, i.e., OPLS3e, has been used throughout the study ( Roos et al., 2019 ) ( Dhanjal et al., 2021 ). Although OPLS3e is the most updated forcefield used nowadays, other popular force fields like AMBER, CHARMM, and GROMOS are also available ( Guvench and MacKerell, 2008 ).…”