Mutations in Influenza a and B Neuraminidase Associated With Oseltamivir Resistance: Contributions of Genomic Surveillance in Brazil

Influenza virus causes flu and leads to a high number of deaths and hospitalizations every year. In severe infections, especially among people at risk for complications, antivirals are key tools for clinical management. Resistance to neuraminidase (NA) inhibitor antivirals, such as oseltamivir, can compromise clinical response to influenza infection. Specific amino acid substitutions in the NA gene of influenza A and B viruses are associated with reduced susceptibility to treatment. This study aimed to verify the occurrence of mutations in the NA-coding gene related to antiviral resistance. NA gene sequences from influenza A and B viruses were analyzed from the GISAID database, referring to ten states in the North and Northeast regions of Brazil, collected between 2014 and 2025. The sequences were screened using FluSurver (GISAID), which maps resistance mutations described by the World Health Organization (WHO), highlighting H275Y (H1N1pdm09), E119V and R292K (H3N2), and T225V (influenza B). Mutation frequencies were assessed by subtype, year, and geographic location. Among 2,920 analyzed NA gene sequences, 1,288 corresponded to influenza A H1N1pdm09, 940 to influenza A H3N2, and 692 to influenza B. Among H1N1pdm09 viruses, mutations Y155H and H275Y were identified, the latter in a sample collected in Pará in 2025. In H3N2, mutation I222V was observed in 21 samples from Pará, all from 2014. In 2021, resistance-associated mutations were detected in Acre, including H274Y and R292K. Mutation E119V was identified in a sample from Paraíba in 2022. Among influenza B viruses, mutations R102K were observed in Amazonas in 2017 and H273N in Pará in 2025. Identifying amino acid substitutions associated with oseltamivir resistance in influenza A and B viruses circulating in Brazil reinforces the importance of continuous genomic monitoring. Incorporating tools such as FluSurver into epidemiological surveillance enables early detection of variants with potential therapeutic impact, supporting control and disease management strategies and the development of new drugs.