GPCR Inhibitors Have Antiviral Properties against JC Polyomavirus Infection.
5-HT2Rs
GPCR agonists/antagonists
JC polyomavirus
PML
cetirizine
paroxetine
progressive multifocal leukoencephalopathy
super-resolution microscopy
β-arrestin
Journal
Viruses
ISSN: 1999-4915
Titre abrégé: Viruses
Pays: Switzerland
ID NLM: 101509722
Informations de publication
Date de publication:
30 Sep 2024
30 Sep 2024
Historique:
received:
30
08
2024
revised:
24
09
2024
accepted:
28
09
2024
medline:
26
10
2024
pubmed:
26
10
2024
entrez:
26
10
2024
Statut:
epublish
Résumé
JC polyomavirus (JCPyV) infects the majority of the population and initially establishes a persistent but asymptomatic infection of the kidneys. In healthy individuals, the infection remains controlled by the host immune system, but for individuals experiencing prolonged immunosuppression, the infection can reactivate and spread to the brain, where it causes progressive multifocal leukoencephalopathy (PML), which is a fatal neurodegenerative disease. Currently, there are no approved therapies to treat PML, and affected individuals suffer rapid motor weakness and cognitive deterioration. To identify novel therapeutic treatments for JCPyV infection, receptor agonists/antagonists identified in a previously published drug screen were evaluated for their antiviral properties. Seven drugs were selected and validated using infectivity assays, and the mechanism of inhibition was further explored for G protein coupled receptor (GPCR)-associated inhibitors due to the role of the GPCR 5-hydroxytryptamine 2 receptors (5-HT
Identifiants
pubmed: 39459893
pii: v16101559
doi: 10.3390/v16101559
pii:
doi:
Substances chimiques
Antiviral Agents
0
Receptors, G-Protein-Coupled
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R15AI144686
Pays : United States
Organisme : NIGMS NIH HHS
ID : R15GM139070
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20GM144265-01A1
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20GM103423
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.