Global update on the susceptibilities of influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2020–2023
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.
Authors
- Áine Rattigan
- Richard J. Webby (ORCID: https://orcid.org/0000-0002-4397-7132)
- Magdi Samaan
- Saira Hussain (ORCID: https://orcid.org/0000-0002-0545-244X)
- Sook Kwan Brown
- Emi Takashita (ORCID: https://orcid.org/0000-0002-9064-4699)
- Clyde Dapat (ORCID: https://orcid.org/0000-0002-7616-4680)
- Rodney S. Daniels (ORCID: https://orcid.org/0000-0003-2818-5089)
- Hui‐Ling Yen (ORCID: https://orcid.org/0000-0003-2493-3609)
- Nicola S. Lewis (ORCID: https://orcid.org/0000-0001-9496-4756)
- Adam Meijer (ORCID: https://orcid.org/0000-0001-8074-7582)
- Larisa V. Gubareva (ORCID: https://orcid.org/0000-0002-3136-5550)
- Mónica Galiano (ORCID: https://orcid.org/0000-0001-7046-3762)
- Angie Lackenby (ORCID: https://orcid.org/0000-0002-1557-0415)
- Elena A. Govorkova (ORCID: https://orcid.org/0000-0001-9067-5682)
- Ian Barr (ORCID: https://orcid.org/0000-0002-7351-418X)
- Rebecca Kondor (ORCID: https://orcid.org/0000-0002-2596-4282)
- Wenqing Zhang (ORCID: https://orcid.org/0000-0002-3636-7133)
- Jing‐Kai Huang (ORCID: https://orcid.org/0000-0002-7187-2653)
- Mira C. Patel (ORCID: https://orcid.org/0000-0002-6237-293X)
- Dayan Wang (ORCID: https://orcid.org/0000-0002-4990-1016)
- Ha T Nguyen (ORCID: https://orcid.org/0000-0002-7987-8718)
- Seiichiro Fujisaki (ORCID: https://orcid.org/0000-0002-6129-8950)
- Janice Lo
- Dmitriy Pereyaslov
Institutions
- Centers for Disease Control and Prevention (US)
- St. Jude Children's Research Hospital (US)
- Department of Health (CN)
- Chinese Center For Disease Control and Prevention (CN)
- The Francis Crick Institute (GB)
- Public Health England (GB)
- National Institute of Infectious Diseases (JP)
- Victorian Infectious Diseases Reference Laboratory (AU)
- National Institute for Public Health and the Environment (NL)
- Peter Doherty Institute (AU)
- World Health Organization (CH)
- National Institute for Viral Disease Control and Prevention (CN)
- Center for Surveillance, Epidemiology, and Laboratory Services (US)
- University of Hong Kong (HK)
Publication Details
- Journal
- Antiviral Research
- Published
- 2025-06-24
- DOI
- https://doi.org/10.1016/j.antiviral.2025.106217
- Citations
- 12
- Primary Topic
- Influenza Virus Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 16.25
Funders
- U.S. Department of Health and Human Services
- Wellcome Trust
- Francis Crick Institute
- American Lebanese Syrian Associated Charities
- Cancer Research UK
- Ministry of Health, Labour and Welfare
- Department of Health and Aged Care, Australian Government
- National Institutes of Health
- Medical Research Council
- Japan Society for the Promotion of Science
- National Key Research and Development Program of China
- National Institute of Allergy and Infectious Diseases