A Computational Insight on the Inhibitory Potential of 8‐Hydroxydihydrosanguinarine (8‐HDS), a Pyridone Containing Analog of Sanguinarine, against SARS CoV2 **

The unprecedented global pandemic of COVID‐19 has created a daunting scenario urging an immediate generation of therapeutic strategy. Interventions to curb the spread of viral infection primarily include setting targets against the virus. 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. Docking studies gave evidence that 8‐hydroxydihydrosanguinarine (8‐HDS), a derivative of sanguinarine, showed 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 also corroborate 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 property of 8‐hydroxydihydrosanguinarine indicates this could be a potential drug. This makes the phyto‐alkaloid a possible therapeutic molecule for anti COVID‐19 drug design.