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.

Methods:
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.

Results:
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.

Conclusions:
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.