Unraveling molecular basis for reduced neuraminidase inhibitors susceptibility in highly pathogenic avian influenza A (H5N1) viruses isolated from chickens in India

The increasing resistance cases in influenza viruses to different classes of antiviral drugs, necessitates the in-depth analysis of molecular interactions governing reduced susceptibility to these drugs. This study explores the molecular basis of neuraminidase inhibitors resistance in avian H5N1 influenza viruses identified in our previous research. Using comprehensive modeling and docking tools, we investigated two isolates--A/chicken/India/85459/2008 (N294S) and A/chicken/WestBengal/142121/2008 (E119A + I117V). The N294S mutation conferred oseltamivir resistance while retaining zanamivir susceptibility, whereas the E119A + I117V mutations led to zanamivir resistance while reducing oseltamivir susceptibility. Molecular interactions analysis unveiled varied fitness levels, hydrogen bonding, and affinity transitions associated with N294S and E119A + I117V mutations. This study provides crucial insights into molecular interactions responsible for reduced susceptibility to neuraminidase inhibitors, which is essential for optimizing antiviral strategies and pandemic preparedness.