Titre :

Identification of potent inhibitors of arenavirus and SARS-CoV-2 exoribonucleases by fluorescence polarization assay.

Auteur(s) :

Hernández, S. [Auteur]
Architecture et fonction des macromolécules biologiques [AFMB]
Feracci, M. [Auteur]
Architecture et fonction des macromolécules biologiques [AFMB]
De Jesus, C. T. [Auteur]
Architecture et fonction des macromolécules biologiques [AFMB]
El Kazzi, P. [Auteur]
Kaci, R. [Auteur]
Garlatti, L. [Auteur]
Mondielli, C. [Auteur]
Evotec [Toulouse]
Bailly, Fabrice [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Cotelle, Philippe [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Touret, F. [Auteur]
Unité des Virus Emergents [UVE]
De Lamballerie, X. [Auteur]
Unité des Virus Emergents [UVE]
Coutard, B. [Auteur]
Decroly, E. [Auteur]
Canard, B. [Auteur]
Ferron, F. [Auteur]
Alvarez, K. [Auteur]
Architecture et fonction des macromolécules biologiques [AFMB]

Titre de la revue :

Antiviral Research

Nom court de la revue :

Antiviral Res

Pagination :

105364

Éditeur :

Elsevier

Date de publication :

2022-08-01

ISSN :

1872-9096

Mot(s)-clé(s) en anglais :

Phosphohydrolaseactivity
Arenaviridae
Coronaviridae
Exoribonuclease activity
Fluorescence polarization
Screening
Inhibitors
IC50
Cellularassays

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Viral exoribonucleases are uncommon in the world of RNA viruses. To date, they have only been identified in the Arenaviridae and the Coronaviridae families. The exoribonucleases of these viruses play a crucial role in the ...
Lire la suite >Viral exoribonucleases are uncommon in the world of RNA viruses. To date, they have only been identified in the Arenaviridae and the Coronaviridae families. The exoribonucleases of these viruses play a crucial role in the pathogenicity and interplay with host innate immune response. Moreover, coronaviruses exoribonuclease is also involved in a proofreading mechanism ensuring the genetic stability of the viral genome. Because of their key roles in virus life cycle, they constitute attractive target for drug design. Here we developed a sensitive, robust and reliable fluorescence polarization assay to measure the exoribonuclease activity and its inhibition in vitro. The effectiveness of the method was validated on three different viral exoribonucleases, including SARS-CoV-2, Lymphocytic Choriomeningitis and Machupo viruses. We performed a screening of a focused library consisting of 113 metal chelators. Hit compounds were recovered with an IC50 at micromolar level. We confirmed 3 hits in SARS-CoV-2 infected Vero-E6 cells.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Date de dépôt :

2024-01-17T22:54:58Z
2025-02-05T08:41:34Z