Screening of Some Ayurvedic Phytochemicals to Identify Potential Inhibitors against SARS-CoV-2 Mpro by In Silico Computational Approach

Background: The classical drug discovery approach demands more than a decade of strenuous exploration and substantial monetary or economic support, which is difficult in pandemic conditions, such as COVID-19. Methods: The main purpose of this work was to ascertain the best inhibitors to combat the SARS-CoV-2 Mpro (PDB ID: 6LU7) target. To achieve this, we conducted a molecular docking screening of 35 phytochemicals from eight different medicinal plants. Using a structurebased drug design of molecular docking, we studied the binding affinities and found 35 molecules that showed greater or identical affinity towards the target than the N3 inhibitor. Additionally, we conducted MD simulations for the 6LU7-schaftoside complex. Results: The docking analysis has identified several promising phytochemicals with great binding attraction towards the key target. The phytoconstituent, schaftoside (-8.7 kcal/mol), demonstrated the most binding attraction with the target via 6 conventional hydrogen bonds. Additionally, 2'-O-methyl cajanone (-8.3 kcal/mol), isoschaftoside (-8.0 kcal/mol), cajaflavonone (-8.0 kcal/mol), and co-crystal N3 inhibitor (-7.8 kcal/mol) also displayed significant binding affinity. Interestingly, schaftoside and 2'-O-methyl cajanone showed the most promising activities with their low binding energies. Conclusion: After thorough analysis, some compounds were found on elite docking sites that resembled drugs and had a harmless ADMET profile. Based on the study, it can be concluded that the compounds mentioned earlier possess the ability to be reused as potent inhibitors against the COVID-19 pandemic.