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Scientific reports2020; 10(1); 10100; doi: 10.1038/s41598-020-66944-4

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

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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Publication Date: 2020-06-22 PubMed ID: 32572069PubMed Central: PMC7308276DOI: 10.1038/s41598-020-66944-4Google Scholar: Lookup
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  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study presents a technique to test potential antiviral drugs on equine cells infected with Equine Arteritis Virus (EAV). It reveals that one existing antiviral drug and two novel inhibitors of a specific enzyme involved in DNA formation can effectively suppress the harmful effects and replication of EAV.

Method and Key Findings

The researchers adopted an in vitro (in the lab) high-throughput testing method using equine dermal cells infected by EAV. The process led to several critical findings:

  • The researchers discovered three compounds that impaired EAV infection in equine cells.
  • The first of these compounds is Ribavirin, an established broad-spectrum antiviral nucleoside analog, which has proved effective against many RNA and DNA viruses in humans and small mammals.
  • The other two are compounds known to inhibit Dihydroorotate Dehydrogenase (DHODH), the fourth enzyme in the production path of pyrimidines, a fundamental unit of DNA.
  • All three molecules suppressed the cytopathic effects associated with EAV infection, significantly inhibiting the replication of the virus and production of infectious particles.

Implications of the Research

The essential implications and potential applications of this study include:

  • Given that Ribavirin is already approved for use in humans and small animals, its proven effectiveness against EAV in this study could offer a readily available treatment option for EAV in larger mammals like horses.
  • The discovery that DHODH inhibiting compounds can suppress EAV replication promises new channels for developing antiviral treatments. With several DHODH inhibitors already in advanced clinical trials for other purposes, it may be possible to repurpose these molecules efficiently for the control of EAV.
  • The study’s findings present new possibilities for managing EAV outbreaks, especially since the vaccination coverage worldwide among equine populations is currently insufficient.
  • This research also contributes to a broader understanding of how RNA viruses operate and could lead to insights applicable to other similar viruses in animals and humans.

Cite This Article

APA
Valle-Casuso JC, Gaudaire D, Martin-Faivre L, Madeline A, Dallemagne P, Pronost S, Munier-Lehmann H, Zientara S, Vidalain PO, Hans A. (2020). Replication of Equine arteritis virus is efficiently suppressed by purine and pyrimidine biosynthesis inhibitors. Sci Rep, 10(1), 10100. https://doi.org/10.1038/s41598-020-66944-4

Publication

Scientific reports
ISSN: 2045-2322
NlmUniqueID: 101563288
Country: England
Language: English
Volume: 10
Issue: 1
Pages: 10100

Researcher Affiliations

Valle-Casuso, José-Carlos
  • Laboratoire de Santé Animale, site de Normandie de l'ANSES, PhEED Unit, 14430, Goustranville, France.
Gaudaire, Delphine
  • Laboratoire de Santé Animale, site de Normandie de l'ANSES, PhEED Unit, 14430, Goustranville, France.
Martin-Faivre, Lydie
  • Laboratoire de Santé Animale, site de Normandie de l'ANSES, PhEED Unit, 14430, Goustranville, France.
Madeline, Anthony
  • Laboratoire de Santé Animale, site de Normandie de l'ANSES, PhEED Unit, 14430, Goustranville, France.
Dallemagne, Patrick
  • Normandie Univ, UNICAEN, CERMN EA4258, 14000, Caen, France.
Pronost, Stéphane
  • LABÉO Frank Duncombe, Normandie Univ, UNICAEN, BIOTARGEN EA7450, 14280, Saint-Contest, France.
Munier-Lehmann, Hélène
  • Institut Pasteur, Unité de Chimie et Biocatalyse, CNRS UMR 3523, 75015, Paris, France.
Zientara, Stephan
  • Université Paris-Est, Laboratoire de Santé Animale, ANSES, INRA, ENVA, UMR 1161 Virologie, 94700, Maisons-Alfort, France.
Vidalain, Pierre-Olivier
  • Equipe Chimie et Biologie, Modélisation et Immunologie pour la Thérapie (CBMIT), Université Paris Descartes, CNRS UMR 8601, 75006, Paris, France.
  • Centre International de Recherche en Infectiologie, Univ Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS UMR5308, ENS de Lyon, F-69007, Lyon, France.
Hans, Aymeric
  • Laboratoire de Santé Animale, site de Normandie de l'ANSES, PhEED Unit, 14430, Goustranville, France. aymeric.hans@anses.fr.

MeSH Terms

  • Animals
  • Antiviral Agents / pharmacology
  • Arterivirus Infections / drug therapy
  • Arterivirus Infections / veterinary
  • Cell Line
  • Cytopathogenic Effect, Viral / drug effects
  • Dihydroorotate Dehydrogenase
  • Equartevirus / metabolism
  • Horse Diseases / virology
  • Horses / genetics
  • Oxidoreductases Acting on CH-CH Group Donors / metabolism
  • Purines / antagonists & inhibitors
  • Purines / biosynthesis
  • Purines / pharmacology
  • Pyrimidines / antagonists & inhibitors
  • Pyrimidines / biosynthesis
  • Pyrimidines / pharmacology
  • RNA / pharmacology
  • Ribavirin / pharmacology
  • Virus Replication / drug effects
  • Virus Replication / physiology

Conflict of Interest Statement

The authors declare no competing interests.

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Citations

This article has been cited 5 times.
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