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Viruses
Volume 14
Issue 1
10.3390/v14010111
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Article

Characterization of the In Vitro and In Vivo Efficacy of Baloxavir Marboxil against H5 Highly Pathogenic Avian Influenza Virus Infection

by
Keiichi Taniguchi
1,2,
Yoshinori Ando
1,
Masanori Kobayashi
1,†,
Shinsuke Toba
1,3,
Haruaki Nobori
1,
Takao Sanaki
1,
Takeshi Noshi
1,
Makoto Kawai
1,
Ryu Yoshida
1,
Akihiko Sato
1,3,
Takao Shishido
1,*,
Akira Naito
1,
Keita Matsuno
3,4,
Masatoshi Okamatsu
2,
Yoshihiro Sakoda
2,4 and
Hiroshi Kida
3,4
1
Shionogi & Co., Ltd., Osaka 561-0825, Japan
2
Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Hokkaido 060-0818, Japan
3
International Institute for Zoonosis Control, Hokkaido University, Hokkaido 001-0020, Japan
4
Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Hokkaido 001-0020, Japan
*
Author to whom correspondence should be addressed.
†
Present address: Organization for Research Initiatives and Development, Doshisha University, Kyoto 610-0394, Japan.
Academic Editor: Hualan Chen
Viruses 2022, 14(1), 111; https://doi.org/10.3390/v14010111
Received: 28 December 2021 / Accepted: 31 December 2021 / Published: 8 January 2022
(This article belongs to the Topic Infectious Diseases)
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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-h 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. View Full-Text
Keywords: baloxavir marboxil; H5N1 highly pathogenic avian influenza virus; viral replication; inhibition; lung inflammation; combination therapy; oseltamivir baloxavir marboxil; H5N1 highly pathogenic avian influenza virus; viral replication; inhibition; lung inflammation; combination therapy; oseltamivir
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MDPI and ACS Style

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

AMA Style

Taniguchi K, Ando Y, Kobayashi M, Toba S, Nobori H, Sanaki T, Noshi T, Kawai M, Yoshida R, Sato A, Shishido T, Naito A, Matsuno K, Okamatsu M, Sakoda Y, Kida H. Characterization of the In Vitro and In Vivo Efficacy of Baloxavir Marboxil against H5 Highly Pathogenic Avian Influenza Virus Infection. Viruses. 2022; 14(1):111. https://doi.org/10.3390/v14010111

Chicago/Turabian Style

Taniguchi, Keiichi, Yoshinori Ando, Masanori Kobayashi, Shinsuke Toba, Haruaki Nobori, Takao Sanaki, Takeshi Noshi, Makoto Kawai, Ryu Yoshida, Akihiko Sato, Takao Shishido, Akira Naito, Keita Matsuno, Masatoshi Okamatsu, Yoshihiro Sakoda, and Hiroshi Kida. 2022. "Characterization of the In Vitro and In Vivo Efficacy of Baloxavir Marboxil against H5 Highly Pathogenic Avian Influenza Virus Infection" Viruses 14, no. 1: 111. https://doi.org/10.3390/v14010111

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