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Lookup NU author(s): Dr Stephen Owens
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 The AuthorsChronic human norovirus (HuNoV) infections in immunocompromised patients result in severe disease, yet approved antivirals are lacking. RNA-dependent RNA polymerase (RdRp) inhibitors inducing viral mutagenesis display broad-spectrum in vitro antiviral activity, but clinical efficacy in HuNoV infections is anecdotal and the potential emergence of drug-resistant variants is concerning. Upon favipiravir (and nitazoxanide) treatment of four immunocompromised patients with life-threatening HuNoV infections, viral whole-genome sequencing showed accumulation of favipiravir-induced mutations which coincided with clinical improvement although treatment failed to clear HuNoV. Infection of zebrafish larvae demonstrated drug-associated loss of viral infectivity and favipiravir treatment showed efficacy despite occurrence of RdRp variants potentially causing favipiravir resistance. This indicates that within-host resistance evolution did not reverse loss of viral fitness caused by genome-wide accumulation of sequence changes. This off-label approach supports the use of mutagenic antivirals for treating prolonged RNA viral infections and further informs the debate surrounding their impact on virus evolution.
Author(s): Kreins AY, Roux E, Pang J, Cheng I, Charles O, Roy S, Mohammed R, Owens S, Lowe DM, Brugha R, Williams R, Howley E, Best T, Davies EG, Worth A, Solas C, Standing JF, Goldstein RA, Rocha-Pereira J, Breuer J
Publication type: Article
Publication status: Published
Journal: Clinical Immunology
Year: 2024
Volume: 259
Print publication date: 01/02/2024
Online publication date: 12/01/2024
Acceptance date: 05/01/2024
Date deposited: 20/02/2024
ISSN (print): 1521-6616
ISSN (electronic): 1521-7035
Publisher: Academic Press Inc.
URL: https://doi.org/10.1016/j.clim.2024.109901
DOI: 10.1016/j.clim.2024.109901
PubMed id: 38218209
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