Global Update on the Susceptibilities of Human Influenza Viruses to Neuraminidase Inhibitors and the Cap-dependent Endonuclease Inhibitor Baloxavir, 2018-2020

Overview

Journal Antiviral Res

Publisher Elsevier

Date 2022 Mar 16

PMID 35292289

Authors

Elena A Govorkova

Emi Takashita

Rod S Daniels

Seiichiro Fujisaki

Lance D Presser

Mira C Patel

Weijuan Huang

Angie Lackenby

Ha T Nguyen

Dmitriy Pereyaslov

Aine Rattigan

Sook Kwan Brown

Magdi Samaan

Kanta Subbarao

Sun Wong

Dayan Wang

Richard J Webby

Hui-Ling Yen

Wenqing Zhang

Adam Meijer

Larisa V Gubareva

Affiliations

Soon will be listed here.

Abstract

Global analysis of the susceptibility of influenza viruses to neuraminidase (NA) inhibitors (NAIs) and the polymerase acidic (PA) inhibitor (PAI) baloxavir was conducted by five World Health Organization Collaborating Centres for Reference and Research on Influenza during two periods (May 2018-May 2019 and May 2019-May 2020). Combined phenotypic and NA sequence-based analysis revealed that the global frequency of viruses displaying reduced or highly reduced inhibition (RI or HRI) or potential to show RI/HRI by NAIs remained low, 0.5% (165/35045) and 0.6% (159/26010) for the 2018-2019 and 2019-2020 periods, respectively. The most common amino acid substitution was NA-H275Y (N1 numbering) conferring HRI by oseltamivir and peramivir in A(H1N1)pdm09 viruses. Combined phenotypic and PA sequence-based analysis showed that the global frequency of viruses showing reduced susceptibility to baloxavir or carrying substitutions associated with reduced susceptibility was low, 0.5% (72/15906) and 0.1% (18/15692) for the 2018-2019 and 2019-2020 periods, respectively. Most (n = 61) of these viruses had I38→T/F/M/S/L/V PA amino acid substitutions. In Japan, where baloxavir use was highest, the rate was 4.5% (41/919) in the 2018-2019 period and most of the viruses (n = 32) had PA-I38T. Zoonotic viruses isolated from humans (n = 32) in different countries did not contain substitutions in NA associated with NAI RI/HRI phenotypes. One A(H5N6) virus had a dual substitution PA-I38V + PA-E199G, which may reduce susceptibility to baloxavir. Therefore, NAIs and baloxavir remain appropriate choices for the treatment of influenza virus infections, but close monitoring of antiviral susceptibility is warranted.

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