In Silico Comparative Screening of Natural Flavonoids as High-Affinity Inhibitors of H5N1 Influenza Neuraminidase

The avian influenza A (H5N1) virus poses a persistent global pandemic threat due to its high pathogenicity and the emergence of resistance to conventional neuraminidase inhibitors such as Oseltamivir. This study employs a computational "virtual screening" approach to evaluate the inhibitory potential of four natural flavonoids Epigallocatechin gallate (EGCG), Quercetin, Kaempferol, and Curcumin against the H5N1 Neuraminidase protein (PDB ID: 3B7E). These ligands were selected for their unique biochemical properties: EGCG (Epigallocatechin gallate) for its dense hydroxyl groups that facilitate hydrogen bonding, Quercetin for its ability to stabilize protein-ligand complexes, Kaempferol for its established antiviral targeting, and Curcumin for its precise geometric fit within enzymatic pockets. Molecular docking simulations conducted via AutoDock Vina revealed that all four natural ligands significantly outperformed Oseltamivir in binding affinity. Notably, EGCG exhibited the strongest binding energy at -9.2 kcal/mol, compared to -6.3 kcal/mol for the clinical control. These findings suggest that natural polyphenolic scaffolds provide a more robust interaction profile for neutralizing H5N1 and warrant urgent in vitro validation.