Phylogeny analysis of Pakistani SARS-CoV2 strains and screening of a list of natural compounds as the antiviral targets for viral M pro protein

Abstract The outbreak of COVID-19 has become a global health concern. The vaccines against SARS-CoV-2 are unable to barricade the reinfection in fully vaccinated individuals. Considering this dilemma, the recent research strategies are focused on the new candidates having antiviral potential with significant and consistent efficacies as well as the least side effects. In this study, we have screened plant-derived phytochemicals, antiviral compounds from PubChem, and natural compounds from the Hamdard products for identification of antiviral therapeutics against Spike (S) glycoprotein and main protease (Mpro) of SARS-CoV-2. All these compounds were screened based on their binding affinities as predicted by molecular docking analysis and compounds having binding affinity values ≤ -10 kcal/mol were considered for analysis. Furthermore, from physicochemical assessment, drug-likeness initially nine compounds were identified as the antiviral targets for the selected viral proteins. Finally, after ADMET analysis and MD simulations, the compound 9064 with the lowest Root Mean Square Deviations (RMSD), Coul-SR interaction energy (-71.53 kJ/mol), and LJ-SR energy (-95.32 kJ/mol) was selected as the most stable drug candidate against COVID-19 main protease Mpro. The selected antiviral compound 9064 is an antioxidant flavonoid (Catechin or Cianidanol), which is previously known to have significant immunomodulatory, anti-inflammatory, and antioxidant properties.