Inhibition of dengue virus infection by trifluoperazine.
Journal
Archives of virology
ISSN: 1432-8798
Titre abrégé: Arch Virol
Pays: Austria
ID NLM: 7506870
Informations de publication
Date de publication:
Nov 2022
Nov 2022
Historique:
received:
28
04
2021
accepted:
17
06
2022
pubmed:
4
8
2022
medline:
15
10
2022
entrez:
3
8
2022
Statut:
ppublish
Résumé
Dengue virus (DENV), a member of the genus Flavivirus, family Flaviviridae, is the most widespread viral pathogen transmitted to humans by mosquitoes. Despite the increased incidence of DENV infection, there are no antiviral drugs available for treatment or prevention. Phenothiazines are heterocyclic compounds with various pharmacological properties that are very adaptable for drug repurposing. In the present report, we analyzed the antiviral activity against DENV and the related Zika virus (ZIKV) of trifluoperazine (TFP), a phenothiazine derivative in clinical use as an antipsychotic and antiemetic agent. TFP exhibited dose-dependent inhibitory activity against the four DENV serotypes and ZIKV in monkey Vero cells at non-cytotoxic concentrations with 50% effective concentration values in the range 1.6-6.4 µM. A similar level of antiviral efficacy was exhibited by TFP against flavivirus infection in the human cell lines A549 and HepG2. Mechanistic studies, performed using time-dependent infectivity assays, real-time RT-PCR, Western blot, and immunofluorescence techniques, indicated that uncoating of the virus during penetration into the cell was the main target for TFP in infected cells, but the compound also exerted a minor effect on a late stage of the virus multiplication cycle. This study demonstrates that TFP, a pharmacologically active phenothiazine, is a selective inhibitor of DENV multiplication in cell culture. Our findings open perspectives for the repositioning of phenothiazines like TFP with a wide spectrum of antiviral efficacy as potential agents for the control of pathogenic flaviviruses.
Identifiants
pubmed: 35920983
doi: 10.1007/s00705-022-05555-y
pii: 10.1007/s00705-022-05555-y
pmc: PMC9362669
doi:
Substances chimiques
Antiemetics
0
Antipsychotic Agents
0
Antiviral Agents
0
Phenothiazines
0
Trifluoperazine
214IZI85K3
phenothiazine
GS9EX7QNU6
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2203-2212Subventions
Organisme : Secretaría de Ciencia y Técnica, Universidad de Buenos Aires
ID : 20020170100363BA
Organisme : Agencia Nacional de Promoción Científica y Tecnológica
ID : PICT 3080
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.
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