In silico evaluation of selected plant-based compounds as potent dual target inhibitors against highly pathogenic avian influenza H5N1 virus.

Abstract

1. Influenza viruses remain a serious global health issue due to their high morbidity and mortality rates. Among them, avian influenza H5N1 virus is highly pathogenic, causing up to 100% mortality in poultry. As the avian influenza H5N1 virus continues to mutate across different regions, understanding multiple viral proteins, particularly the mutated haemagglutinin (HA) and neuraminidase (NA), is crucial for effective control.2. In this study, dual-target inhibitors capable of neutralising both HA and NA were developed, and a comprehensive in silico analysis was performed on different variants collected over the past decade. Structural modelling revealed conserved domains in NA (A0A1I9QM14, China) and HA (A0A0A0V4U2, Bali), which were selected for ligand docking.3. Twenty active compounds, traditionally used as natural feed additives in broiler chicken diets, were screened using protein-ligand docking, ADME profiling, and molecular dynamics (MD) simulations. Quercetin and luteolin emerged as promising dual-target inhibitors, showing high binding affinity, drug-likeness, and favourable toxicity profiles. The binding free energy (ΔG = -8 ± 0.2 kcal/mol) from docking studies confirmed their inhibitory potential against avian influenza H5N1 virus HA and NA.4. The results demonstrated that virtual screening of natural compounds can effectively identify those effective against influenza virus surface proteins. This integrative computational-experimental strategy supported the development of novel plant-derived antiviral agents with potential applications for disease control.