Titre :

Vemurafenib Inhibits Acute and Chronic Enterovirus Infection by Affecting Cellular Kinase Phosphatidylinositol 4-Kinase Type IIIβ.

Auteur(s) :

Laajala, Mira [Auteur]
University of Jyväskylä [JYU]
Zwaagstra, Marleen [Auteur]

Martikainen, Mari [Auteur]
University of Jyväskylä [JYU]
Nekoua, Magloire Pandoua [Auteur]
Laboratoire de virologie - ULR 3610
Benkahla, Mehdi [Auteur]
Laboratoire de Virologie - ULR 3610 [Laboratoire de Virologie]
Sane, Famara [Auteur]
Laboratoire de virologie - ULR 3610
Gervais, Emily [Auteur]
Colorado State University [Fort Collins] [CSU]
Campagnola, Grace [Auteur]
Colorado State University [Fort Collins] [CSU]
Honkimaa, Anni [Auteur]
University of Tampere [Finland]
Sioofy-Khojine, Amir-Babak [Auteur]
University of Tampere [Finland]
Hyöty, Heikki [Auteur]
University of Tampere [Finland]
Ojha, Ravi [Auteur]
Department of Virology [Helsinki]
Bailliot, Marie [Auteur]
Department of Virology [Helsinki]
Balistreri, Giuseppe [Auteur]
Department of Virology [Helsinki]
Peersen, Olve [Auteur]
Colorado State University [Fort Collins] [CSU]
Hober, Didier [Auteur]
Laboratoire de virologie - ULR 3610
Van Kuppeveld, Frank [Auteur]
Universiteit Utrecht / Utrecht University [Utrecht]
Marjomäki, Varpu [Auteur]
University of Jyväskylä [JYU]

Titre de la revue :

Microbiol Spectr

Nom court de la revue :

Microbiol Spectr

Numéro :

11

Pagination :

e0055223

Date de publication :

2023-07-15

ISSN :

2165-0497

Mot(s)-clé(s) en anglais :

enterovirus
drug repurposing
chronic infection
antiviral
acute infection

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Enteroviruses are one of the most abundant viruses causing mild to serious acute infections in humans and also contributing to chronic diseases like type 1 diabetes. Presently, there are no approved antiviral drugs against ...
Lire la suite >Enteroviruses are one of the most abundant viruses causing mild to serious acute infections in humans and also contributing to chronic diseases like type 1 diabetes. Presently, there are no approved antiviral drugs against enteroviruses. Here, we studied the potency of vemurafenib, an FDA-approved RAF kinase inhibitor for treating BRAFV600E mutant-related melanoma, as an antiviral against enteroviruses. We showed that vemurafenib prevented enterovirus translation and replication at low micromolar dosage in an RAF/MEK/ERK-independent manner. Vemurafenib was effective against group A, B, and C enteroviruses, as well as rhinovirus, but not parechovirus or more remote viruses such as Semliki Forest virus, adenovirus, and respiratory syncytial virus. The inhibitory effect was related to a cellular phosphatidylinositol 4-kinase type IIIβ (PI4KB), which has been shown to be important in the formation of enteroviral replication organelles. Vemurafenib prevented infection efficiently in acute cell models, eradicated infection in a chronic cell model, and lowered virus amounts in pancreas and heart in an acute mouse model. Altogether, instead of acting through the RAF/MEK/ERK pathway, vemurafenib affects the cellular PI4KB and, hence, enterovirus replication, opening new possibilities to evaluate further the potential of vemurafenib as a repurposed drug in clinical care.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
CHU Lille

Collections :

• Laboratoire de virologie - ULR 3610

Date de dépôt :

2024-01-17T22:01:31Z
2024-02-12T08:59:07Z