Free Energy Landscapes and Residue Network Analysis for Six SARS-CoV-2 Targets in Complex with Plausible Phytochemical Inhibitors from Withania Somnifera: 1 µS Molecular Dynamics Simulations
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The pandemic is here to stay- evident from the second wave that is severely affecting global population. Though vaccination is now available, the population size restricts its efficacy, especially in the third world countries. Therefore, to avoid a third wave, natural preventive therapeutics are the need of the hour. In this work the efficiency of phytochemicals from Withania somnifera to bind to a total of six SARS-CoV-2 targets have been shown.1 µs molecular dynamics simulations and essential dynamic analyses shed light on the changes induced by the phytochemicals and highlights their multipotent capabilities- 27-Hydroxywithanolide B was able to bind to three targets. Relative free energy of binding for all the phytochemicals were calculated by MM/PBSA. Minimum energy structures were extracted from their free energy landscapes and were subjected to PSN-ENM-NMA and network centrality analysis. Results showed that the phytochemical binding changes the residue-residue interaction network. Network communities increase while hubs and links decrease. Metapath rewiring occurs through residues Phe456 in spike protein, Thr26 and Tyr118 in main protease, Val49 and Phe156 in NSP3, Leu98 in NSP9, Leu4345 in NSP10, Phe440 and Phe843 in NSP12. This work tries to understand the mechanism of possible inhibition by the phytochemicals to combat SARS-CoV-2 with their capability of targeting multiple proteins. The insight from this study can be of great relevance to explore the changes in network properties induced by reported potential inhibitors against SARS-CoV-2 targets.
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Methanolic extract of Withania somnifera (0.125-2 mg/ml) inhibits acid production, tolerance, and biofilm production of oral microflora Streptococcus sobrinus and Streptococcus mutans at sub-MIC levels in vitro.
“Methanolic extract of WS (0.125-2 mg/ml) reportedly inhibited acid production, tolerance, and biofilm production of oral microflora such as Streptococcus sobrinus and Streptococcus mutans at sub-Minimal inhibitory concentrations (MIC) levels in vitro [253].”
From Withania somnifera (L.) Dunal (Ashwagandha): A comprehensive review on ethnopharmacology, pharmacotherapeutics, biomedicinal and toxicological aspects (2021) · cites this paper as [253]
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- Authors
- Parida, P. K., Paul, D., & Chakravorty, D.
- Affiliations
- Novel Techsciences (OPC) Private Limited
- Venue
- ChemRxiv
- Publisher
- American Chemical Society (ACS)
- Published
- 2021-04-28
- ISSN
- 2573-2293 (ISSN-L)
- OpenAlex
- W3157516877
- Cited by
- 0
- References
- 77
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- ChemRxiv (acceptedVersion, cc-by-nc-nd)
- Royal College of Surgeons in Ireland (submittedVersion, cc-by-nc-nd)
- Topics
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Complementary and alternative medicine › Phytochemicals and Medicinal Plants
- Keywords
- SARS-CoV-2, Withania somnifera, phytochemical inhibitors, free energy landscape, residue interaction networks, network centrality, spike protein, main protease, NSP3, nsp9, nsp10, nsp12, MM-PBSA binding free energy, essential dynamics
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