Phytochemicals from AYUSH-64 screened against main protease and spike protein of Omicron variant of SARS-CoV-2 using ensemble docking approach

The current wave of the COVID-19 pandemic is due to the B.1.1.529 variant of the SARS-CoV-2 designated as Omicron. AYUSH-64 a poly herbal drug developed by Central Council for Research in Ayurvedic Sciences (CCRAS) has been recommended by Ministry of AYUSH in asymptomatic, mild to moderate COVID-19 patients. One of the earlier in-silico studies had shown the binding of the constituents of AYUSH-64 to the SARS-CoV-2 drug targets. The current study proposes to understand their binding of the top four phytochemicals to the same drug targets of the Omicron variant with respect to crucial drug targets, main protease (Mpro) and receptor binding domain (RBD) of spike protein. An enhanced molecular docking methodology, namely, ensemble docking has been used in the particular study. Using MD simulations and clustering approach it was observed that the Mpro and RBD-spike of Omicron variant of SARS-CoV-2 tends to attain 4 and 8 conformational respectively. Docking these individual conformations with akummicine-N-oxide, akummiginone, echitamidine-n-oxide, and echitaminic acid revealed that the binding was better in case of the mutant as compared to the wild type. Hence, it can be inferred that, these phytochemicals from AYUSH-64 formulation may have the potential to act against the Omicron variant of SARS-CoV-2.