Contributors: Virologie UMR1161 (VIRO); École nationale vétérinaire d'Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES); BioImagerie Photonique – Photonic BioImaging (UTechS PBI); Institut Pasteur Paris (IP)-Université Paris Cité (UPCité); Centre Hospitalier Universitaire d'Angers (CHU Angers); PRES Université Nantes Angers Le Mans (UNAM); University of Edinburgh (Edin.); Chimie et Biocatalyse - Chemistry and Biocatalysis (group); Institut Pasteur Paris (IP)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Institut des cellules souches pour le traitement et l'étude des maladies monogéniques (I-STEM); Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon; This work was funded by the French National Research Institute for Agriculture, Food and Environment (INRAE), the Ecole Nationale Vétérinaire d’Alfort (Enva), the Fonds Eperons and the Institut Français du Cheval et de l’Equitation (IFCE) and the DIM1Health (Ile de France, NB). The Roslin Institute received funding from the Biotechnology and Biological Sciences Research Council (UK). The UtechS PBI, part of the France–BioImaging infrastructure network (ANR-10–INSB–04; Investments for the Future) received funding from the Région Île-de-France (DIM1Health) and the Institut Pasteur.; ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010)
نبذة مختصرة : International audience ; Outbreaks of West Nile virus (WNV) occur periodically, affecting both human and equine populations. There are no vaccines for humans, and those commercialised for horses do not have sufficient coverage. Specific antiviral treatments do not exist. Many drug discovery studies have been conducted, but since rodent or primate cell lines are normally used, results cannot always be transposed to horses. There is thus a need to develop relevant equine cellular models. Here, we used induced pluripotent stem cells to develop a new in vitro model of WNV-infected equine brain cells suitable for microplate assay, and assessed the cytotoxicity and antiviral activity of forty-one chemical compounds. We found that one nucleoside analog, 2’C-methylcytidine, blocked WNV infection in equine brain cells, whereas other compounds were either toxic or ineffective, despite some displaying anti-viral activity in human cell lines. We also revealed an unexpected proviral effect of statins in WNV-infected equine brain cells. Our results thus identify a potential lead for future drug development and underscore the importance of using a tissue- and species-relevant cellular model for assessing the activity of antiviral compounds.
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