Detection of influenza A(H3N2) viruses exhibiting reduced susceptibility to the novel cap-dependent endonuclease inhibitor baloxavir in Japan, December 2018

doi:10.2807/1560-7917.ES.2019.24.3.1800698

. 2019 Jan;24(3):1800698.

doi: 10.2807/1560-7917.ES.2019.24.3.1800698.

Detection of influenza A(H3N2) viruses exhibiting reduced susceptibility to the novel cap-dependent endonuclease inhibitor baloxavir in Japan, December 2018

Emi Takashita¹, Chiharu Kawakami², Hiroko Morita¹, Rie Ogawa¹, Seiichiro Fujisaki¹, Masayuki Shirakura¹, Hideka Miura¹, Kazuya Nakamura¹, Noriko Kishida¹, Tomoko Kuwahara¹, Keiko Mitamura³, Takashi Abe⁴, Masataka Ichikawa⁵, Masahiko Yamazaki⁶, Shinji Watanabe¹, Takato Odagiri¹; Influenza Virus Surveillance Group of Japan⁷

Affiliations

¹ Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
² Yokohama City Institute of Public Health, Kanagawa, Japan.
³ Eiju General Hospital, Tokyo, Japan.
⁴ Abe Children's Clinic, Kanagawa, Japan.
⁵ Ichikawa Children's Clinic, Kanagawa, Japan.
⁶ Zama Children's Clinic, Kanagawa, Japan.
⁷ The members of the group are listed at the end of the article.

PMID: 30670142
PMCID: PMC6344841
DOI: 10.2807/1560-7917.ES.2019.24.3.1800698

Detection of influenza A(H3N2) viruses exhibiting reduced susceptibility to the novel cap-dependent endonuclease inhibitor baloxavir in Japan, December 2018

Emi Takashita et al. Euro Surveill. 2019 Jan.

. 2019 Jan;24(3):1800698.

doi: 10.2807/1560-7917.ES.2019.24.3.1800698.

Authors

Affiliations

¹ Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
² Yokohama City Institute of Public Health, Kanagawa, Japan.
³ Eiju General Hospital, Tokyo, Japan.
⁴ Abe Children's Clinic, Kanagawa, Japan.
⁵ Ichikawa Children's Clinic, Kanagawa, Japan.
⁶ Zama Children's Clinic, Kanagawa, Japan.
⁷ The members of the group are listed at the end of the article.

PMID: 30670142
PMCID: PMC6344841
DOI: 10.2807/1560-7917.ES.2019.24.3.1800698

Abstract

The novel cap-dependent endonuclease inhibitor baloxavir marboxil was approved for the treatment of influenza virus infection in Japan in February 2018. Two influenza A(H3N2) viruses carrying an I38T substitution in the polymerase acidic subunit (PA) were detected in baloxavir-treated children in December 2018. This mutation is known to confer reduced susceptibility to baloxavir, and the two mutant viruses exhibited 76- and 120-fold reduced susceptibility to baloxavir.

Keywords: Influenza virus; baloxavir acid; baloxavir marboxil; cap-dependent endonuclease inhibitor; resistant.

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Conflict of interest statement

Conflict of interest: None declared.

Figures

**Figure**
Detection of influenza viruses, Japan, September 2015–December 2018 (n = 28,093)

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References

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[1] Koszalka P, Tilmanis D, Hurt AC. Influenza antivirals currently in late-phase clinical trial. Influenza Other Respir Viruses. 2017;11(3):240-6. 10.1111/irv.12446 - DOI - PMC - PubMed

[2] Koszalka P, Tilmanis D, Hurt AC. Influenza antivirals currently in late-phase clinical trial. Influenza Other Respir Viruses. 2017;11(3):240-6. 10.1111/irv.12446 - DOI - PMC - PubMed

[3] Hayden FG, Sugaya N, Hirotsu N, Lee N, de Jong MD, Hurt AC, et al. Baloxavir marboxil for uncomplicated influenza in adults and adolescents. N Engl J Med. 2018;379(10):913-23. 10.1056/NEJMoa1716197 - DOI - PubMed

[4] Hayden FG, Sugaya N, Hirotsu N, Lee N, de Jong MD, Hurt AC, et al. Baloxavir marboxil for uncomplicated influenza in adults and adolescents. N Engl J Med. 2018;379(10):913-23. 10.1056/NEJMoa1716197 - DOI - PubMed

[5] Omoto S, Speranzini V, Hashimoto T, Noshi T, Yamaguchi H, Kawai M, et al. Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil. Sci Rep. 2018;8(1):9633. 10.1038/s41598-018-27890-4 - DOI - PMC - PubMed

[6] Omoto S, Speranzini V, Hashimoto T, Noshi T, Yamaguchi H, Kawai M, et al. Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil. Sci Rep. 2018;8(1):9633. 10.1038/s41598-018-27890-4 - DOI - PMC - PubMed

[7] Takashita E, Morita H, Ogawa R, Nakamura K, Fujisaki S, Shirakura M, et al. Susceptibility of influenza viruses to the novel cap-dependent endonuclease inhibitor baloxavir marboxil. Front Microbiol. 2018;9(3026):3026. 10.3389/fmicb.2018.03026 - DOI - PMC - PubMed

[8] Takashita E, Morita H, Ogawa R, Nakamura K, Fujisaki S, Shirakura M, et al. Susceptibility of influenza viruses to the novel cap-dependent endonuclease inhibitor baloxavir marboxil. Front Microbiol. 2018;9(3026):3026. 10.3389/fmicb.2018.03026 - DOI - PMC - PubMed

[9] Aoki FY, Boivin G, Roberts N. Influenza virus susceptibility and resistance to oseltamivir. Antivir Ther. 2007;12(4 Pt B):603-16. - PubMed

[10] Aoki FY, Boivin G, Roberts N. Influenza virus susceptibility and resistance to oseltamivir. Antivir Ther. 2007;12(4 Pt B):603-16. - PubMed

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Detection of influenza A(H3N2) viruses exhibiting reduced susceptibility to the novel cap-dependent endonuclease inhibitor baloxavir in Japan, December 2018

Affiliations

Detection of influenza A(H3N2) viruses exhibiting reduced susceptibility to the novel cap-dependent endonuclease inhibitor baloxavir in Japan, December 2018

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Affiliations

Abstract

Conflict of interest statement

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