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

Sci Rep. 2020 Jun 22;10(1):10100. doi: 10.1038/s41598-020-66944-4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

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

Substances

  • Antiviral Agents
  • Dihydroorotate Dehydrogenase
  • Purines
  • Pyrimidines
  • Ribavirin
  • RNA
  • Oxidoreductases Acting on CH-CH Group Donors
  • pyrimidine