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

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By G.M.

Highlights

• Antiviral susceptibility to NA inhibitors and PA inhibitor baloxavir was determined for seasonal and zoonotic influenza viruses circulating globally during 2020–2023.

• Low global frequencies (0.1-0.2%) of seasonal influenza viruses with reduced or highly reduced inhibition by NAI inhibitors were observed as in previous years.

• Low global frequencies of seasonal influenza viruses (∼ 0.1%) with reduced susceptibility to baloxavir were observed, with the rate in Japan elevated (3.3%) in 2022–2023, as has been seen previously.

• For zoonotic viruses, 2.7% contained genetic markers associated with reduced or highly reduced inhibition to NA inhibitors and none contained markers associated with reduced susceptibility for baloxavir.

• For the treatment of influenza, NA inhibitors and baloxavir remain suitable.


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.

Source: Antiviral Research, https://www.sciencedirect.com/science/article/abs/pii/S0166354225001433?via%3Dihub

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