Replication of Equine arteritis virus is efficiently suppressed by purine and pyrimidine biosynthesis inhibitors

嘌呤和嘧啶生物合成抑制剂可有效抑制马动脉炎病毒的复制

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作者:José-Carlos Valle-Casuso #, Delphine Gaudaire #, Lydie Martin-Faivre, Anthony Madeline, Patrick Dallemagne, Stéphane Pronost, Hélène Munier-Lehmann, Stephan Zientara, Pierre-Olivier Vidalain, Aymeric Hans

Abstract

RNA viruses are responsible for a large variety of animal infections. Equine Arteritis Virus (EAV) is a positive single-stranded RNA virus member of the family Arteriviridae from the order Nidovirales like the Coronaviridae. EAV causes respiratory and reproductive diseases in equids. Although two vaccines are available, the vaccination coverage of the equine population is largely insufficient to prevent new EAV outbreaks around the world. In this study, we present a high-throughput in vitro assay suitable for testing candidate antiviral molecules on equine dermal cells infected by EAV. Using this assay, we identified three molecules that impair EAV infection in equine cells: the broad-spectrum antiviral and nucleoside analog ribavirin, and two compounds previously described as inhibitors of dihydroorotate dehydrogenase (DHODH), the fourth enzyme of the pyrimidine biosynthesis pathway. These molecules effectively suppressed cytopathic effects associated to EAV infection, and strongly inhibited viral replication and production of infectious particles. Since ribavirin is already approved in human and small animal, and that several DHODH inhibitors are in advanced clinical trials, our results open new perspectives for the management of EAV outbreaks.

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