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Criblage d’inhibiteurs de l’interaction virus/hôte [LP]PxY/Nedd4 : une cible antivirale à large spectre

Abstract : Broad-spectrum antiviral identification is considered as one of the major aims of theactual virology research and one strategy consists in targeting virus/host interaction. Using theAlphaScreen® technology and the adenoviral model protein VI/Nedd4-2, we performed highthroughputbiochemical screening targeting the [LP]PxY/Nedd4 interaction, a commoninteraction of different virus families. We identified candidate inhibitors from a librarycompound approved by health agencies. We tested, characterized and validated the antiviraleffect of those compounds on two very different virus families. Indeed, compounds C9(Sulconazole) and C4 (Flunarizine) decrease replication of the adenovirus, a DNA nonenvelopedvirus and the replication of the Marburg virus, an RNA enveloped virus from theFilovirus family. Taken together, those results permit us to validate the [LP]PxY/Nedd4interaction as good target for a broad spectrum antiviral and to propose the “repositioning” ofcompounds C4 and C9 as antivirals. Moreover, we have synthesized new analogues from C9showing similar effect on AdV replication compared to the original molecule (C9). Inconclusion, our work on developing new broad-spectrum antivirals highlights the possibilityto use imidazole derivatives as a new class of antiviral compounds.
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Sisley Austin. Criblage d’inhibiteurs de l’interaction virus/hôte [LP]PxY/Nedd4 : une cible antivirale à large spectre. Immunologie. Université de Bordeaux, 2015. Français. ⟨NNT : 2015BORD0340⟩. ⟨tel-01675983v2⟩

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