Antiviral Susceptibility of Highly Pathogenic Avian Influenza A(H5N1) Viruses Circulating Globally in 2022-2023

Konstantin Andreev; Jeremy C Jones; Patrick Seiler; Ahmed Kandeil; Jasmine C M Turner; Subrata Barman; Adam M Rubrum; Richard J Webby; Elena A Govorkova

doi:10.1093/infdis/jiad418

Antiviral Susceptibility of Highly Pathogenic Avian Influenza A(H5N1) Viruses Circulating Globally in 2022-2023

J Infect Dis. 2023 Sep 28:jiad418. doi: 10.1093/infdis/jiad418. Online ahead of print.

Authors

Konstantin Andreev¹, Jeremy C Jones¹, Patrick Seiler¹, Ahmed Kandeil¹, Jasmine C M Turner¹, Subrata Barman¹, Adam M Rubrum¹, Richard J Webby¹, Elena A Govorkova¹

Affiliation

¹ Department of Infectious Diseases, St. Jude Children's Research Hospital; Memphis, TN, USA.

PMID: 37770028
DOI: 10.1093/infdis/jiad418

Abstract

The antiviral susceptibility of currently circulating (2022-2023) highly pathogenic avian influenza (HPAI) A(H5N1) viruses was assessed by genotypic and phenotypic approaches. The frequency of neuraminidase (NA) and polymerase acidic (PA) substitutions associated with reduced inhibition by NA inhibitors (NAIs) (21/2698, 0.78%) or by the PA inhibitor baloxavir (14/2600, 0.54%) was low. Phenotypic testing of 22 clade 2.3.2.1a and 2.3.4.4b viruses revealed broad susceptibility to NAIs and baloxavir concluding that most contemporary HPAI A(H5N1) viruses retain susceptibility to antiviral drugs. Novel NA-K432E and NA-T438I substitutions (N2 numbering) were identified at elevated frequencies (104/2698, 3.85%) and caused reduced zanamivir and peramivir inhibition.

Keywords: Avian influenza; H5N1; antiviral resistance; baloxavir; clade 2.3.4.4b; neuraminidase; neuraminidase inhibitors; polymerase; risk assessment; zanamivir.