Purine and pyrimidine biosynthesis inhibitors efficiently suppress equine arteritis virus replication
Abstract
Background: 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 Equartiviridae from the order Nidovirales like the Coronaviridae family. EAV causes respiratory and reproductive diseases in equids. Although two vaccines are available, the vaccination coverage of the equine population is insufficient to prevent new EAV outbreaks around the world.
Objectives: To identify therapeutic agents which might be useful in outbreak control and limit the viral dissemination.
Study design: In vitro model.
Methods: An in vitro model of EAV infection assay based in the quantification of ATP by luminometry was established. This system allows evaluation of the cytotoxicity and cellular protection of molecules and collect supernatant to measure viral replication levels of EAV by RT-qPCR.
Results: Using this assay, three molecules that impaired EAV infection in equine cells were identified: 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 with EAV infection, and strongly inhibited viral replication and production of infectious particles.
Main limitations: In vitro effects may not be present in vivo.
Conclusions: Since ribavirin is already approved in humans and small animals, and several DHODH inhibitors are in advanced clinical trials, these results may lead to the identification of molecules that impair EVA viral replication for clinical use.