Genomic Variability in the Neuraminidase Gene and Antiviral Resistance of Influenza A(H1N1)pdm09 Virus Isolated from Acute Respiratory Infection Patients in Shiraz, Iran (2023–2024)

Background The 2009 Influenza A(H1N1)pdm09 pandemic caused significant global morbidity and mortality. Mutations in the neuraminidase (NA) gene can influence viral pathogenicity, immune evasion, and resistance to antiviral drugs, necessitating continuous molecular surveillance to guide antiviral development. Methods From November 2023 to December 2024, 300 respiratory samples were collected from patients with acute respiratory infections in Shiraz, Iran. Real-Time PCR identified Influenza A(H1N1)pdm09, followed by conventional PCR amplification and sequencing of the NA gene. Mutations and resistance to neuraminidase inhibitors (oseltamivir, zanamivir) were assessed using MEGA 11, I-TASSER modeling, and AutoDock Vina docking. Phylogenetic analysis was performed to evaluate genetic relationships. Results Of the 300 samples, 14 were positive for Influenza A(H1N1)pdm09. Sequence analysis identified 26 NA gene mutations, with N44S, I106V, and N200S detected in 3, 4, and 3 isolates, respectively. No isolates showed the H275Y mutation, indicating sensitivity to oseltamivir and zanamivir. Phylogenetically, the isolates were highly similar to A/California/07/2009, clustering with 2008–2009 global strains from Luxembourg and Yamagata. Conclusion Despite significant genetic variability in the NA gene, current antiviral therapies remain effective against these isolates. This study underscores the importance of ongoing surveillance to detect emerging mutations that could impact influenza management globally.