Abstract
Avian influenza is a disease that primarily affects birds but is rarely transmitted to humans. The fatality rate of infection with the highly pathogenic H5N1 avian influenza virus is particularly high. Oseltamivir is known to be an effective antiviral agent against both human and avian influenza. However, an Asn-to-Ser mutation in the N1 neuraminidase has been reported to confer resistance to oseltamivir, and accurate analysis to identify the cause of drug resistance is needed. In this study, fragment molecular orbital (FMO) calculations were performed to gain insight into the electronic mechanism of oseltamivir resistance in avian influenza neuraminidase. The FMO method is an innovative approach that enables quantum mechanical calculations of entire biomolecules, such as proteins. The amino acid residues involved in ligand binding can be identified through the interfragment interaction energies (IFIEs) derived from FMO calculations. The IFIE results suggest that one of the factors contributing to oseltamivir resistance in the N294S mutant is a reduction in the interaction energy between oseltamivir and ASP151, ARG152, and GLU277 in the N1 mutant. The Asn-to-Ser mutation at position 294 does not directly have a significant impact.
