Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Jan;24(3):1800666.
doi: 10.2807/1560-7917.ES.2019.24.3.1800666.

Assessing baloxavir susceptibility of influenza viruses circulating in the United States during the 2016/17 and 2017/18 seasons

Larisa V Gubareva  1 , Vasiliy P Mishin  1 , Mira C Patel  1   2 , Anton Chesnokov  1 , Ha T Nguyen  1   2 , Juan De La Cruz  1   2 , Sarah Spencer  1 , Angela P Campbell  1 , Mallory Sinner  3 , Heather Reid  3 , Rebecca Garten  1 , Jackie M Katz  1 , Alicia M Fry  1 , John Barnes  1 , David E Wentworth  1
Affiliations

Assessing baloxavir susceptibility of influenza viruses circulating in the United States during the 2016/17 and 2017/18 seasons

Larisa V Gubareva et al. Euro Surveill. 2019 Jan.

Abstract

The anti-influenza therapeutic baloxavir targets cap-dependent endonuclease activity of polymerase acidic (PA) protein. We monitored baloxavir susceptibility in the United States with next generation sequencing analysis supplemented by phenotypic one-cycle infection assay. Analysis of PA sequences of 6,891 influenza A and B viruses collected during 2016/17 and 2017/18 seasons showed amino acid substitutions: I38L (two A(H1N1)pdm09 viruses), E23G (two A(H1N1)pdm09 viruses) and I38M (one A(H3N2) virus); conferring 4-10-fold reduced susceptibility to baloxavir.

Keywords: Cap-dependent endonuclease inhibitor; drug resistance; influenza; influenza surveillance; next generation sequencing; phenotypic testing; polymerase acidic protein.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: None declared.

References

    1. U.S. Food and Drug Administration (FDA). FDA approves new drug to treat influenza. Silver Spring: FDA; 2018. Available from: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm624226.htm.
    1. Heo YA. Baloxavir: First Global Approval. Drugs. 2018;78(6):693-7. 10.1007/s40265-018-0899-1 - DOI - PubMed
    1. XOFLUZATM Drug label. San Francisco: Genentech USA, Inc.; 2018. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210854s000lbl.pdf.
    1. 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
    1. 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

MeSH terms