The natural way forward: Molecular dynamics simulation analysis of phytochemicals from Indian medicinal plants as potential inhibitors of SARS-CoV-2 targets.
The pandemic COVID-19 has become a global panic-forcing life towards a compromised "new normal." Antiviral therapy against SARS-CoV-2 is still lacking. Thus, development of natural inhibitors as a prophylactic measure is an attractive strategy. In this context, this work explored phytochemicals as potential inhibitors for SARS-CoV-2 by performing all atom molecular dynamics simulations using high performance computing for 8 rationally screened phytochemicals from Withania somnifera and Azadirachta indica and two repurposed drugs docked with the spike glycoprotein and the main protease of SARS-CoV-2. These phytochemicals were rationally screened from 55 Indian medicinal plants in our previous work. MM/PBSA, principal component analysis (PCA), dynamic cross correlation matrix (DCCM) plots and biological pathway enrichment analysis were performed to reveal the therapeutic efficacy of these phytochemicals. The results revealed that Withanolide R (-141.96 KJ/mol) and 2,3-Dihydrowithaferin A (-87.60 KJ/mol) were with the lowest relative free energy of binding for main protease and the spike proteins respectively. It was also observed that the phytochemicals exhibit a remarkable multipotency with the ability to modulate various human biological pathways especially pathways in cancer. Conclusively we suggest that these compounds need further detailed in vivo experimental evaluation and clinical validation to implement them as potent therapeutic agents for combating SARS-CoV-2.
['Parida|Pratap Kumar|PK|https://orcid.org/0000-0002-8193-335X', 'Paul|Dipak|D|https://orcid.org/0000-0002-5664-4601', 'Chakravorty|Debamitra|D|https://orcid.org/0000-0002-1520-0780']
D000998:Antiviral Agents D031601:Azadirachta D000086382:COVID-19 D000086782:Coronavirus 3C Proteases D007194:India D056004:Molecular Dynamics Simulation D064209:Phytochemicals D010946:Plants, Medicinal D000086402:SARS-CoV-2 D064370:Spike Glycoprotein, Coronavirus D032341:Withania
molecular dynamics simulation phytochemicals SARS-CoV-2 spike main protease India relative free binding energy