Replication of Equine arteritis virus is efficiently suppressed by purine and pyrimidine biosynthesis inhibitors. 2020

José-Carlos Valle-Casuso, and Delphine Gaudaire, and Lydie Martin-Faivre, and Anthony Madeline, and Patrick Dallemagne, and Stéphane Pronost, and Hélène Munier-Lehmann, and Stephan Zientara, and Pierre-Olivier Vidalain, and Aymeric Hans
Laboratoire de Santé Animale, site de Normandie de l'ANSES, PhEED Unit, 14430, Goustranville, France.

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.

UI MeSH Term Description Entries
D007240 Equartevirus A genus of the family ARTERIVIRIDAE. Alphaarterivirus,Arteritis Virus, Equine,Infectious Arteritis Virus, Equine,Equine Arteritis Virus,Equine Infectious Arteritis Virus,Infectious Arteritis Virus of Horses,Alphaarteriviruses,Arteritis Viruses, Equine,Equarteviruses,Equine Arteritis Viruses
D011687 Purines A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.
D011743 Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D003588 Cytopathogenic Effect, Viral Visible morphologic changes in cells infected with viruses. It includes shutdown of cellular RNA and protein synthesis, cell fusion, release of lysosomal enzymes, changes in cell membrane permeability, diffuse changes in intracellular structures, presence of viral inclusion bodies, and chromosomal aberrations. It excludes malignant transformation, which is CELL TRANSFORMATION, VIRAL. Viral cytopathogenic effects provide a valuable method for identifying and classifying the infecting viruses. Cytopathic Effect, Viral,Viral Cytopathogenic Effect,Cytopathic Effects, Viral,Cytopathogenic Effects, Viral,Effect, Viral Cytopathic,Effect, Viral Cytopathogenic,Effects, Viral Cytopathic,Effects, Viral Cytopathogenic,Viral Cytopathic Effect,Viral Cytopathic Effects,Viral Cytopathogenic Effects
D006734 Horse Diseases Diseases of domestic and wild horses of the species Equus caballus. Equine Diseases,Disease, Equine,Disease, Horse,Diseases, Equine,Diseases, Horse,Equine Disease,Horse Disease
D006736 Horses Large, hoofed mammals of the family EQUIDAE. Horses are active day and night with most of the day spent seeking and consuming food. Feeding peaks occur in the early morning and late afternoon, and there are several daily periods of rest. Equus caballus,Equus przewalskii,Horse, Domestic,Domestic Horse,Domestic Horses,Horse,Horses, Domestic
D000090722 Dihydroorotate Dehydrogenase An oxidoreductase that catalyzes the conversion of DIHYDROOROTATE to orotate with QUINONE as an electron acceptor in the biosynthesis of PYRIMIDINES. DHODH,DHOO-Dehydrogenase-U,Dihydro-Orotate Dehydrogenase,Dihydro-Orotate-Cytochrome C Reductase,Dihydroorotate Dehydrogenase (Ubiquinone),Dihydroorotate Dehydrogenase Type A,Dihydroorotate Dehydrogenase Type B,Dihydroorotate Dehydrogenase Type C,Dihydroorotate-Ubiquinone Oxidoreductase,DHODase A,DHODase B,A, DHODase,B, DHODase,C Reductase, Dihydro-Orotate-Cytochrome,DHOO Dehydrogenase U,Dehydrogenase, Dihydro-Orotate,Dehydrogenase, Dihydroorotate,Dihydro Orotate Cytochrome C Reductase,Oxidoreductase, Dihydroorotate-Ubiquinone,Reductase, Dihydro-Orotate-Cytochrome C
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral

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