Characterization of the in Vitro and in Vivo Efficacy of Baloxavir Marboxil against h5 Highly Pathogenic Avian Influenza Virus Infection

Version 1 : Received: 5 November 2021 / Approved: 9 November 2021 / Online: 9 November 2021 (14:43:02 CET)
Version 2 : 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.

Taniguchi, K.; Ando, Y.; Kobayashi, M.; Toba, S.; Nobori, H.; Sanaki, T.; Noshi, T.; Kawai, M.; Yoshida, R.; Sato, A.; et al. Characterization of the In Vitro and In Vivo Efficacy of Baloxavir Marboxil against H5 Highly Pathogenic Avian Influenza Virus Infection. Viruses 2022, 14, 111, doi:10.3390/v14010111. Taniguchi, K.; Ando, Y.; Kobayashi, M.; Toba, S.; Nobori, H.; Sanaki, T.; Noshi, T.; Kawai, M.; Yoshida, R.; Sato, A.; et al. Characterization of the In Vitro and In Vivo Efficacy of Baloxavir Marboxil against H5 Highly Pathogenic Avian Influenza Virus Infection. Viruses 2022, 14, 111, doi:10.3390/v14010111.

Abstract

Human infections caused by the H5 highly pathogenic avian influenza virus (HPAIV) sporadically threaten public health. The susceptibility of HPAIVs to baloxavir acid (BXA), a new class of inhibitors for the influenza virus cap-dependent endonuclease, has been confirmed in vitro, but it has not yet been fully characterized. Here, the efficacy of BXA against HPAIVs, including recent H5N8 variants, was assessed in vitro. 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 in comparison with seasonal and other zoonotic strains. Compared with oseltamivir phosphate (OSP), BXM monotherapy in mice infected with the H5N1 HPAIV clinical isolate, the A/Hong Kong/483/1997 strain, also caused a significant reduction in viral titers in the lungs, brains, and kidneys, thereby preventing acute lung inflammation and reducing mortality. Furthermore, compared with BXM or OSP monotherapy, combination treatments with BXM and OSP using a 48-hour delayed treatment model showed a more potent effect on viral replication in the organs, accompanied by improved survival. In conclusion, BXM has a potent antiviral efficacy against H5 HPAIV infections.

Keywords

baloxavir marboxil; H5N1 highly pathogenic avian influenza virus; viral replication; inhibition; lung inflammation; combination therapy; oseltamivir

Subject

Biology and Life Sciences, Virology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Received: 12 January 2022
Commenter: Keiichi Taniguchi
Commenter's Conflict of Interests: Author

Comment: Our manuscript has been accepted, so we want to update files before peer-review.

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