Abrogating the nsp10–nsp16 switching mechanisms in SARS-CoV-2 by phytochemicals from Withania somnifera: a molecular dynamics study

Vuai, Said A. H.; Onokaa, Isaac; Sahini, Mtabazi G.; Swai, Hulda S.; Shadrack, Daniel M.

dc.creator	Vuai, Said A. H.
dc.creator	Onokaa, Isaac
dc.creator	Sahini, Mtabazi G.
dc.creator	Swai, Hulda S.
dc.creator	Shadrack, Daniel M.
dc.date	2022-03-09T12:01:49Z
dc.date	2022-03-09T12:01:49Z
dc.date	2021
dc.date.accessioned	2022-10-20T13:09:31Z
dc.date.available	2022-10-20T13:09:31Z
dc.identifier	Vuai, S. A., Onoka, I., Sahini, M. G., Swai, H. S., & Shadrack, D. M. (2021). Abrogating the nsp10–nsp16 switching mechanisms in SARS-CoV-2 by phytochemicals from Withania somnifera: a molecular dynamics study. Molecular Simulation, 47(16), 1372-1380.
dc.identifier	DOI: 10.1080/08927022.2021.1974432
dc.identifier	http://hdl.handle.net/20.500.12661/3469
dc.identifier.uri	http://hdl.handle.net/20.500.12661/3469
dc.description	Abstract. The full-text article is available at https://doi.org/10.1080/08927022.2021.1974432
dc.description	The search for therapeutic small molecules and vaccines for Covid-19 treatment is an urgent but evolving topic. The virus has claimed over 3,782,490 lives (as of 12 June 2021), with the figure expected to rise due to the high versatility of the SAR-CoV-2 variant. Therapeutic options based on SARS-CoV-2 inhibitor are essential. Withanolides have a long history in traditional medicines with versatile biological properties including antiviral activities. In this study, the inhibitory potential of withanolides from Withania somnifera (Ashwagandha) against SARS-CoV-2 non-structural protein 10 (nsp10) was investigated by employing atomistic in silico methods viz molecular docking, molecular dynamics and binding free energy calculations. Investigated Withania somnifera compounds demonstrated binding affinity to the nsp10 and in its complex form, that is, nsp10-nsp16 heterodimer. Two withanolides; withanoside IV and withanoside V isolated from the roots of Withania somnifera demonstrated strong inhibition with binding free energies of −29.5 and −29.1 kJ/mol, respectively. Molecular dynamics and binding free energy ascertained the stability of withanoside IV. Water molecules, although known to play an important role in mediating biological systems, herein, water was found to have a repulsive binding effect to some residues, suggesting that the binding of withanoside IV would require dewetting of the nsp10 or displacing the water to bulk solvents. Interestingly, residues in the nsp10 that are responsible for forming stable interaction at the nsp10–nsp16 were found to be strongly interacting with withanoside IV, hence weakening the nsp10–nsp16 interaction and recognition. Further in vitro and in vivo experiments are recommended to validate the anti-SARS-COV-2 potential of these phytochemicals.
dc.language	en
dc.publisher	Taylor & Francis
dc.subject	SAR-CoV-2
dc.subject	Covid-19
dc.subject	Withania somnifera
dc.subject	Molecular dynamics
dc.subject	Natural products
dc.subject	Ashwagandha
dc.subject	withanolides
dc.title	Abrogating the nsp10–nsp16 switching mechanisms in SARS-CoV-2 by phytochemicals from Withania somnifera: a molecular dynamics study
dc.type	Article