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Characterization of the In Vitro and In Vivo Efficacy of Baloxavir Marboxil against the H5 Highly Pathogenic Avian Influenza Virus Infection
: Received: 5 November 2021 / Approved: 9 November 2021 / Online: 9 November 2021 (14:43:02 CET)
: Received: 11 January 2022 / Approved: 12 January 2022 / Online: 12 January 2022 (13:18:58 CET)
A peer-reviewed article of this Preprint also exists.
Journal reference: Viruses 2022
Human infections with the H5 highly pathogenic avian influenza virus (HPAIV) sporadically threatens public health. The susceptibility of HPAIVs to baloxavir acid (BXA), which is a new class of inhibitor for the influenza virus cap-dependent endonuclease, has been confirmed in vitro, but has not yet been characterized fully. Here, the efficacy of BXA against HPAIVs, including recent H5N8 variants in vitro was assessed. The antiviral efficacy of baloxavir marboxil (BXM) in H5N1 virus-infected mice was also investigated. BXA exhibited similar in vitro activities against H5N1, H5N6, and H5N8 variants tested to those of seasonal and other zoonotic strains. BXM monotherapy in mice infected with the H5N1 HPAIV clinical isolate; A/Hong Kong/483/1997 (H5N1) strain, also caused a significant reduction in viral titers in the lungs, brains, and kidneys, followed by prevention of acute lung inflammation and improvement of mortality compared with oseltamivir phosphate (OSP). Furthermore, combination treatments with BXM and OSP, using a 48-hour delayed treatment model showed a more potent effect on viral replication in organs, accompanied by improved survival compared to BXM or OSP monotherapy. From each test, no resistant virus (e.g., I38T in the PA) emerged in any BXM-treated mouse. These results therefore support the conclusion that BXM has potent antiviral efficacy against H5 HPAIV infections.
baloxavir marboxil; H5N1 highly pathogenic avian influenza virus; viral replication; inhibition; lung inflammation; combination therapy; oseltamivir
LIFE SCIENCES, Virology
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