Molnupiravir increases SARS-CoV-2 genome diversity and complexity: A case-control cohort study.
Humans
SARS-CoV-2
/ genetics
Antiviral Agents
/ therapeutic use
Genome, Viral
Hydroxylamines
/ pharmacology
COVID-19 Drug Treatment
Male
Female
Case-Control Studies
Middle Aged
Cytidine
/ analogs & derivatives
Aged
Adult
Whole Genome Sequencing
Genetic Variation
Uridine
/ pharmacology
COVID-19
/ virology
Mutation
SARS‐CoV‐2
complexity
diversity
molnupiravir
quasispecies
tixagevimab/cilgavimab
transition
transversion
Journal
Journal of medical virology
ISSN: 1096-9071
Titre abrégé: J Med Virol
Pays: United States
ID NLM: 7705876
Informations de publication
Date de publication:
May 2024
May 2024
Historique:
revised:
18
04
2024
received:
05
03
2024
accepted:
22
04
2024
medline:
6
5
2024
pubmed:
6
5
2024
entrez:
6
5
2024
Statut:
ppublish
Résumé
Molnupiravir, an oral direct-acting antiviral effective in vitro against SARS-CoV-2, has been largely employed during the COVID-19 pandemic, since December 2021. After marketing and widespread usage, a progressive increase in SARS-CoV-2 lineages characterized by a higher transition/transversion ratio, a characteristic signature of molnupiravir action, appeared in the Global Initiative on Sharing All Influenza Data (GISAID) and International Nucleotide Sequence Database Collaboration (INSDC) databases. Here, we assessed the drug effects by SARS-CoV-2 whole-genome sequencing on 38 molnupiravir-treated persistently positive COVID-19 outpatients tested before and after treatment. Seventeen tixagevimab/cilgavimab-treated outpatients served as controls. Mutational analyses confirmed that SARS-CoV-2 exhibits an increased transition/transversion ratio seven days after initiation of molnupiravir. Moreover we observed an increased G->A ratio compared to controls, which was not related to apolipoprotein B mRNAediting enzyme, catalytic polypeptide-like (APOBEC) activity. In addition, we demonstrated for the first time an increased diversity and complexity of the viral quasispecies.
Substances chimiques
molnupiravir
YA84KI1VEW
Antiviral Agents
0
Hydroxylamines
0
Cytidine
5CSZ8459RP
Uridine
WHI7HQ7H85
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e29642Subventions
Organisme : European Commission
Organisme : Ministero della Salute
Organisme : Ministero della Salute: Ricerca Corrente-linea 1, and 5 per Mille-Progetto
ID : 5M-2020-23682104
Organisme : European Commission: HORIZON-INFRA-2021-EMERGENCY-01
ID : 101046203
Informations de copyright
© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.
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