Global update on the susceptibilities of human influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2017–2018

Emi Takashita*, Rod S. Daniels, Seiichiro Fujisaki, Vicki Gregory, Larisa V. Gubareva, Weiijuan Huang, Aeron C. Hurt, Angie Lackenby, Ha T. Nguyen, Dmitriy Pereyaslov, Merryn Roe, Magdi Samaan, Kanta Subbarao, Herman Tse, Dayan Wang, Hui Ling Yen, Wenqing Zhang, Adam Meijer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

86 Citations (Scopus)
29 Downloads (Pure)

Abstract

The global analysis of neuraminidase inhibitor (NAI) susceptibility of influenza viruses has been conducted since the 2012–13 period. In 2018 a novel cap-dependent endonuclease inhibitor, baloxavir, that targets polymerase acidic subunit (PA) was approved for the treatment of influenza virus infection in Japan and the United States. For this annual report, the susceptibilities of influenza viruses to NAIs and baloxavir were analyzed. A total of 15409 viruses, collected by World Health Organization (WHO) recognized National Influenza Centers and other laboratories between May 2017 and May 2018, were assessed for phenotypic NAI susceptibility by five WHO Collaborating Centers (CCs). The 50% inhibitory concentration (IC50) was determined for oseltamivir, zanamivir, peramivir and laninamivir. Reduced inhibition (RI) or highly reduced inhibition (HRI) by one or more NAIs was exhibited by 0.8% of viruses tested (n = 122). The frequency of viruses with RI or HRI has remained low since this global analysis began (2012–13: 0.6%; 2013–14: 1.9%; 2014–15: 0.5%; 2015–16: 0.8%; 2016–17: 0.2%). PA gene sequence data, available from public databases (n = 13523), were screened for amino acid substitutions associated with reduced susceptibility to baloxavir (PA E23G/K/R, PA A36V, PA A37T, PA I38F/M/T/L, PA E119D, PA E199G): 11 (0.08%) viruses possessed such substitutions. Five of them were included in phenotypic baloxavir susceptibility analysis by two WHO CCs and IC50 values were determined. The PA variant viruses showed 6–17-fold reduced susceptibility to baloxavir. Overall, in the 2017–18 period the frequency of circulating influenza viruses with reduced susceptibility to NAIs or baloxavir was low, but continued monitoring is important.

Original languageEnglish
Article number104718
JournalAntiviral Research
Volume175
Early online date28 Jan 2020
DOIs
Publication statusPublished - Mar 2020

Bibliographical note

Funding Information: The Atlanta CC received grants [# AMD-77 and # AMD-102 ] from the Advanced Molecular Detection (AMD) Program , CDC , to establish the next generation sequencing and bioinformatics support for influenza viruses. The Beijing CC received grants from National Key Research and Development Program of China [ 2016YFD0500208 ]. The London CC is supported by the Francis Crick Institute receiving core funding from Cancer Research UK [ FC001030 ], the Medical Research Council [ FC001030 ] and the Wellcome Trust [ FC001030 ]. The Melbourne CC is supported by the Australian Government, Department of Health. The Tokyo CC is supported by Grants-in-Aid for Emerging and Re-emerging Infectious Diseases from the Ministry of Health, Labour and Welfare, Japan [ 10110400 ] and by JSPS KAKENHI Grant number 18K10036.

Open Access: This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).

Publisher Copyright: © 2020 The Authors. Published by Elsevier B.V.

Citation: Emi Takashita, Rod S. Daniels, Seiichiro Fujisaki, Vicki Gregory, Larisa V. Gubareva, Weiijuan Huang, Aeron C. Hurt, Angie Lackenby, Ha T. Nguyen, Dmitriy Pereyaslov, Merryn Roe, Magdi Samaan, Kanta Subbarao, Herman Tse, Dayan Wang, Hui-Ling Yen, Wenqing Zhang, Adam Meijer, Global update on the susceptibilities of human influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2017–2018, Antiviral Research, Volume 175, 2020, 104718, ISSN 0166-3542,

DOI: https://doi.org/10.1016/j.antiviral.2020.104718.

Keywords

  • Baloxavir
  • Influenza
  • Neuraminidase inhibitor
  • Resistance
  • Surveillance
  • Susceptibility

Fingerprint

Dive into the research topics of 'Global update on the susceptibilities of human influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2017–2018'. Together they form a unique fingerprint.

Cite this