8-Hydroxydihydrosanguinarine (8-HDS), a pyridone containing analogue of sanguinarine, can be a potential inhibitor of S protein and M protease of SARS CoV2 Insights from computational studies

The unprecedented global pandemic of COVID-19 has created a daunting scenario urging an immediate generation of therapeutic strategy. Viral inhibitory potential of Pyridone ring containing analogues was already accounted for several infectious viruses and suggested for being significant in case of present COVID-19. Thus, pyridone ring containing 8-HDS is subjected for its inhibitory prospective in the present study for SARS-CoV2. <b>Methods:</b> Here in this study we target S protein to obstruct the viral attachment and entry and also the M pro to prevent the viral replication. For this purpose, the interaction of S protein and M pro with phytocompounds, sanguinarine and eugenol, and their derivatives were studied using computational tools. <b>Results:</b> It is evident from the docking studies that 8-Hydroxydihydrosanguinarine, a derivative of sanguinarine, exhibits maximum binding affinity with both the targets. The binding energies of the ligand with S protein and M pro scored to be ΔGb-9.4 Kcal/mol and ΔGb-10.3 Kcal/mol respectively. MD simulation studies depict that the phytocompound could effectively cause structural perturbations in the targets which would affect their functions. 8-Hydroxydihydrosanguinarine distorts the α-helix in the secondary structure of M pro and RBD site of S protein. Protein-protein interaction study in presence of 8-hydroxydihydrosanguinarine (8-HDS) also corroborates the above findings which indicate that this polyphenol interferes in the coupling of S Protein and ACE2. The alterations in protonation of M pro suggest that the protein structure undergoes significant structural changes at neutral pH. ADME (Physicochemical, Lipophilicity, Water Solubility, Pharmacokinetics, Drug-likeness) property of 8-HDS suggests that this could be a potential drug. <b>Conclusions:</b> Our research via computational tools establishes that 8-HDS can be an efficient inhibitor in blocking viral infection. This makes the phyto-alkaloid a possible therapeutic molecule for anti COVID-19 drug design. Thus it can prove to be a potential molecule in therapeutic drug development against COVID-19.