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. 2025 Sep:241:106217.
doi: 10.1016/j.antiviral.2025.106217. Epub 2025 Jun 24.

Global update on the susceptibilities of influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2020-2023

Saira Hussain  1 , Adam Meijer  2 , Elena A Govorkova  3 , Clyde Dapat  4 , Larisa V Gubareva  5 , Ian G Barr  4 , Sook Kwan Brown  4 , Rod S Daniels  6 , Seiichiro Fujisaki  7 , Monica Galiano  6 , Weijuan Huang  8 , Rebecca J Kondor  5 , Angie Lackenby  9 , Nicola Lewis  6 , Janice Lo  10 , Ha T Nguyen  5 , Mira C Patel  5 , Dmitriy Pereyaslov  11 , Aine Rattigan  6 , Magdi Samaan  11 , Dayan Wang  8 , Richard J Webby  3 , Hui-Ling Yen  12 , Wenqing Zhang  11 , Emi Takashita  7
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Free article

Global update on the susceptibilities of influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2020-2023

Saira Hussain et al. Antiviral Res. 2025 Sep.
Free article

Abstract

Antiviral susceptibility of influenza viruses is monitored by the World Health Organization Global Influenza Surveillance and Response System. This study describes a global analysis of the susceptibility of influenza viruses to neuraminidase (NA) inhibitors (NAIs, oseltamivir, zanamivir, peramivir, laninamivir) and the cap-dependent endonuclease inhibitor (CENI, baloxavir) for three periods (May to May for 2020-2021, 2021-2022 and 2022-2023). In particular, global influenza activity declined significantly in 2020-2021 and 2021-2022 when compared to the pre-pandemic period of COVID-19. Combined phenotypic and NA sequence-based analysis revealed that the global frequency of seasonal influenza viruses with reduced or highly reduced inhibition (RI/HRI) by NAIs remained low, 0.09% (2/2224), 0.12% (27/23465) and 0.23% (124/53917) for 2020-2021, 2021-2022 and 2022-2023, respectively. As in previous years, NA-H275Y in A(H1N1)pdm09 viruses was the most frequent substitution causing HRI by oseltamivir and peramivir. Sequence-based analysis of polymerase acidic (PA) protein supplemented with phenotypic testing revealed low global frequencies of seasonal influenza viruses with reduced susceptibility (RS) to baloxavir, 0.07% (1/1376), 0.05% (9/18380) and 0.12% (48/39945) for 2020-2021, 2021-2022 and 2022-2023, respectively; commonly associated substitutions were PA-I38T/M/L. In Japan, the rate was 3.3% (16/488) during 2022-2023, with 11 A(H3N2) viruses having PA-I38T/M substitutions. For zoonotic viruses, 2.7% (3/111) contained substitutions, one each NA-H275Y, NA-S247N and NA-N295S, associated with RI/HRI NAI phenotypes, and none contained PA substitutions associated with RS to baloxavir. In conclusion, the great majority of seasonal and zoonotic influenza viruses remained susceptible to NAIs and CENI baloxavir.

Keywords: Antiviral; Baloxavir; Influenza; Neuraminidase inhibitor; Polymerase inhibitor; Reduced susceptibility.

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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.

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