Toggle Main Menu Toggle Search

Open Access padlockePrints

Favipiravir induces HuNoV viral mutagenesis and infectivity loss with clinical improvement in immunocompromised patients

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.

Publication metadata

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.


DOI: 10.1016/j.clim.2024.109901

PubMed id: 38218209


Altmetrics provided by Altmetric


Funder referenceFunder name
GOSH Children’s Charity
KUL starting grant (STG/21/028)
NIHR UCL/UCLH Biomedical Research Centre
Rosetrees Trust
the Wellcome Trust [222096/Z/20/Z]
Research Foundation Flanders (FWO) [Project Number:11K7922N]
the National Institute for Health Research (NIHR) [NIHR301575]