Efficacy of favipiravir against influenza virus resistant to both baloxavir and neuraminidase inhibitors.
Animals
Mice
Humans
Oseltamivir
/ pharmacology
Neuraminidase
/ genetics
Influenza A Virus, H1N1 Subtype
/ genetics
Antiviral Agents
/ pharmacology
Pyridones
/ pharmacology
Enzyme Inhibitors
/ pharmacology
Triazines
/ pharmacology
Guanidines
/ pharmacology
Influenza, Human
/ drug therapy
Drug Resistance, Viral
/ genetics
Journal
The Journal of antimicrobial chemotherapy
ISSN: 1460-2091
Titre abrégé: J Antimicrob Chemother
Pays: England
ID NLM: 7513617
Informations de publication
Date de publication:
05 07 2023
05 07 2023
Historique:
received:
29
12
2022
accepted:
19
04
2023
pmc-release:
20
05
2024
medline:
6
7
2023
pubmed:
20
5
2023
entrez:
20
5
2023
Statut:
ppublish
Résumé
Widespread resistance of influenza viruses to neuraminidase (NA) inhibitor or polymerase inhibitor, baloxavir, is a major public health concern. The amino acid mutations R152K in NA and I38T in polymerase acidic (PA) are responsible for resistance to NA inhibitors and baloxavir, respectively. We generated recombinant A(H1N1)pdm09 viruses possessing NA-R152K, PA-I38T or both mutations by using a plasmid-based reverse genetics system, characterized their virological properties in vitro and in vivo, and examined whether oseltamivir, baloxavir and favipiravir are effective against these mutant viruses. The three mutant viruses showed similar or superior growth kinetics and virulence to those of wild-type virus. Although oseltamivir and baloxavir blocked the replication of the wild-type virus in vitro, oseltamivir and baloxavir failed to suppress the replication of the NA-R152K and PA-I38T viruses in vitro, respectively. Mutant virus possessing both mutations grew in the presence of oseltamivir or baloxavir in vitro. Baloxavir treatment protected mice from lethal infection with wild-type or NA-R152K virus, but failed to protect mice from lethal infection with PA-I38T or PA-I38T/NA-R152K virus. Favipiravir treatment protected mice from lethal infection with all viruses tested, whereas oseltamivir treatment did not protect at all. Our findings indicate that favipiravir should be used to treat patients with suspected baloxavir-resistant virus infection.
Identifiants
pubmed: 37209424
pii: 7174982
doi: 10.1093/jac/dkad145
pmc: PMC10320054
doi:
Substances chimiques
Oseltamivir
20O93L6F9H
baloxavir
4G86Y4JT3F
favipiravir
EW5GL2X7E0
Neuraminidase
EC 3.2.1.18
Antiviral Agents
0
Pyridones
0
Enzyme Inhibitors
0
Triazines
0
Guanidines
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1649-1657Subventions
Organisme : NIAID NIH HHS
ID : HHSN272201400008C
Pays : United States
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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