Sofosbuvir Selects for Drug-Resistant Amino Acid Variants in the Zika Virus RNA-Dependent RNA-Polymerase Complex In Vitro.
Amino Acid Substitution
Animals
Antiviral Agents
/ pharmacology
Binding Sites
Carcinoma, Hepatocellular
/ pathology
Cell Line, Tumor
Chlorocebus aethiops
Humans
Inhibitory Concentration 50
Liver Neoplasms
/ pathology
Models, Molecular
Molecular Dynamics Simulation
Point Mutation
Protein Binding
Protein Conformation
RNA, Viral
/ biosynthesis
RNA-Dependent RNA Polymerase
/ antagonists & inhibitors
Selection, Genetic
Sofosbuvir
/ pharmacology
Vero Cells
Viral Nonstructural Proteins
/ antagonists & inhibitors
Virus Replication
/ drug effects
Zika Virus
/ drug effects
Zika virus
genetic barrier
in vitro selection
molecular dynamics
sofosbuvir
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
06 Mar 2021
06 Mar 2021
Historique:
received:
26
01
2021
revised:
23
02
2021
accepted:
03
03
2021
entrez:
3
4
2021
pubmed:
4
4
2021
medline:
1
5
2021
Statut:
epublish
Résumé
The nucleotide analog sofosbuvir, licensed for the treatment of hepatitis C, recently revealed activity against the Zika virus (ZIKV) in vitro and in animal models. However, the ZIKV genetic barrier to sofosbuvir has not yet been characterized. In this study, in vitro selection experiments were performed in infected human hepatoma cell lines. Increasing drug pressure significantly delayed viral breakthrough (
Identifiants
pubmed: 33800884
pii: ijms22052670
doi: 10.3390/ijms22052670
pmc: PMC7962015
pii:
doi:
Substances chimiques
Antiviral Agents
0
NS5 protein, zika virus
0
RNA, Viral
0
Viral Nonstructural Proteins
0
RNA-Dependent RNA Polymerase
EC 2.7.7.48
Sofosbuvir
WJ6CA3ZU8B
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca
ID : cod. 2017BMK8JR
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