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Emerg Infect Dis . Antiviral Susceptibility of Influenza A(H5N1) Clade 2.3.2.1c and 2.3.4.4b Viruses from Humans, 2023-2024

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  • Emerg Infect Dis . Antiviral Susceptibility of Influenza A(H5N1) Clade 2.3.2.1c and 2.3.4.4b Viruses from Humans, 2023-2024

    Emerg Infect Dis


    . 2025 Mar 10;31(4).
    doi: 10.3201/eid3104.241820. Online ahead of print.
    Antiviral Susceptibility of Influenza A(H5N1) Clade 2.3.2.1c and 2.3.4.4b Viruses from Humans, 2023-2024

    Philippe Noriel Q Pascua, Anton Chesnokov, Ha T Nguyen, Han Di, Juan De La Cruz, Yunho Jang, Andrei A Ivashchenko, Alexandre V Ivachtchenko, Erik A Karlsson, Borann Sar, Chin Savuth, Timothy M Uyeki, Charles Todd Davis, Larisa V GubarevaAbstract

    During 2023-2024, highly pathogenic avian influenza A(H5N1) viruses from clade 2.3.2.1c caused human infections in Cambodia and from clade 2.3.4.4b caused human infections in the Americas. We assessed the susceptibility of those viruses to approved and investigational antiviral drugs. Except for 2 viruses isolated from Cambodia, all viruses were susceptible to M2 ion channel-blockers in cell culture-based assays. In the neuraminidase inhibition assay, all viruses displayed susceptibility to neuraminidase inhibitor antiviral drugs oseltamivir, zanamivir, peramivir, laninamivir, and AV5080. Oseltamivir was ≈4-fold less potent at inhibiting the neuraminidase activity of clade 2.3.4.4b than clade 2.3.2.1c viruses. All viruses were susceptible to polymerase inhibitors baloxavir and tivoxavir and to polymerase basic 2 inhibitor pimodivir with 50% effective concentrations in low nanomolar ranges. Because drug-resistant viruses can emerge spontaneously or by reassortment, close monitoring of antiviral susceptibility of H5N1 viruses collected from animals and humans by using sequence-based analysis supplemented with phenotypic testing is essential.

    Keywords: antimicrobial resistance; antiviral; drug resistance; influenza; influenza A(H5N1); polymerase inhibitors; respiratory infections; viruses; zoonoses; zoonotic infections.

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