Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Aug:358:199599.
doi: 10.1016/j.virusres.2025.199599. Epub 2025 Jun 26.

A 15-year study of neuraminidase mutations and the increasing of S247N mutation in Spain

Iván Sanz-Muñoz  1 , Alejandro Martín-Toribio  2 , Adrián García-Concejo  3 , Irene Arroyo-Hernantes  4 , Marina Toquero-Asensio  4 , Javier Sánchez-Martínez  4 , Carla Rodríguez-Crespo  4 , Silvia Rojo-Rello  5 , Marta Domínguez-Gil  6 , Eduardo Tamayo-Gómez  7 , Marta Hernández-Pérez  2 , José M Eiros  8
Affiliations

A 15-year study of neuraminidase mutations and the increasing of S247N mutation in Spain

Iván Sanz-Muñoz et al. Virus Res. 2025 Aug.

Abstract

The therapeutic arsenal against influenza is extremely limited and resistance often arises due to the emergence of mutations, especially in the neuraminidase (NA) gene. This study aimed to evaluate the evolution of NA mutations over 15 years in Spain. To do so, we used the GISAID database from which we downloaded a total of 11,125 influenza A(H1N1)pdm09, A(H3N2), B/Victoria and B/Yamagata NA virus sequences, and analyzed the resistance mutations using FluSurver software. Our results showed that the occurrence of NA resistance mutations remained constant in the four viruses during the 15 seasons evaluated, being around 0.5-5 %. Most of the resistance was found in the A(H1N1)pdm09 subtype (around 70 %), especially from the 2023-2024 season onwards, when a significant increase in the occurrence of S247N mutation was observed. The occurrence of this type of mutation before 2022 was rare, but in the 2023-2024 season a total of 44 influenza viruses harboring S247N mutations were detected, while in the other years, only two cases were observed. Some studies have described a significant increase in this mutation over the past two seasons and although it appears to confer only slightly reduced inhibition to oseltamivir, its increase is noteworthy and should be a reason for increased their vigilance.

Keywords: Antiviral drugs; Influenza; Oseltamivir; Resistance mutations; S247N.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

References

    1. Akand E.H., Downard K.M. Mechanisms of antiviral resistance in influenza neuraminidase revealed by a mass spectrometry based phylonumerics approach. Mol. Phylogenet. Evol. 2019;135:286–296. - PubMed
    1. CDC. CDC A(H5N1) bird flu response update November 18, 2024 [Internet]. 2024 [cited 21th May 2025]. Available: https://www.cdc.gov/bird-flu/spotlights/h5n1-response-11152024.html.
    1. Chong Y., Matsumoto S., Kang D., Ikematsu H. Consecutive influenza surveillance of neuraminidase mutations and neuraminidase inhibitor resistance in Japan. Influenza Other Respir. Viruses. 2019;13(2):115. - PMC - PubMed
    1. Dong G., Peng C., Luo J., Wang C., Han L., Wu B., et al. Adamantane-resistant influenza a viruses in the world (1902-2013): frequency and distribution of M2 gene mutations. PLoS One. 2015;10(3) - PMC - PubMed
    1. Duwe S.C., Milde J., Heider A., Wedde M., Schweiger B., Dürrwald R. Increase of synergistic secondary antiviral mutations in the evolution of A(H1N1)pdm09 influenza virus neuraminidases. Viruses. 2024;16(7):1109. - PMC - PubMed

MeSH terms

LinkOut - more resources