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Characterization of the In Vitro and In Vivo Efficacy of Baloxavir Marboxil against H5 Highly Pathogenic Avian Influenza Virus Infection
Title: | Characterization of the In Vitro and In Vivo Efficacy of Baloxavir Marboxil against H5 Highly Pathogenic Avian Influenza Virus Infection |
Authors: | Taniguchi, Keiichi Browse this author | Ando, Yoshinori Browse this author | Kobayashi, Masanori Browse this author | Toba, Shinsuke Browse this author | Nobori, Haruaki Browse this author | Sanaki, Takao Browse this author | Noshi, Takeshi Browse this author | Kawai, Makoto Browse this author | Yoshida, Ryu Browse this author | Sato, Akihiko Browse this author | Shishido, Takao Browse this author | Naito, Akira Browse this author | Matsuno, Keita Browse this author →KAKEN DB | Okamatsu, Masatoshi Browse this author →KAKEN DB | Sakoda, Yoshihiro Browse this author →KAKEN DB | Kida, Hiroshi Browse this author →KAKEN DB |
Keywords: | baloxavir marboxil | viral replication | inhibition | lung inflammation | combination therapy | oseltamivir |
Issue Date: | Jan-2022 |
Publisher: | MDPI |
Journal Title: | Viruses-Basel |
Volume: | 14 |
Issue: | 1 |
Start Page: | 111 |
Publisher 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-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. |
Type: | article |
URI: | http://hdl.handle.net/2115/84183 |
Appears in Collections: | 人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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