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

jose-carlos Valle-Casuso; Delphine Gaudaire; Lydie Martin-Faivre; anthony madeline; Patrick Dallemagne; Stephane Pronost; Helene Munier-Lehmann; Stephan Zientara; Pierre-Olivier Vidalain; Aymeric Hans

To verify that ribavirin, IPPA17-A04 and GAC50 actually block EAV replication, viral genome copies 180 were quantified at 48 h.p.i. Culture supernatants of infected ED cells treated or not with the 181 compounds at different concentrations were analyzed by RT-qPCR. Results showed that ribavirin at 5 182 and 10 µg/ml significantly reduced the number of EAV genome copies in culture supernatants 183 compared to the untreated infected cells ( Figure 4A ). EAV replication was totally blocked at 20 µg/ml 184 as determined by comparison with the initial inoculum quantified at 1 h.p.i. These results confirmed 185 that ribavirin impairs EAV replication in ED cells, thus explaining the positive effect on cell survival. In 186 parallel, we also measured viral genome copies present in the supernatant of infected cells treated 187 with pyrimidine biosynthesis inhibitors. As expected, IPPA17-A04 and GAC50 both reduced the 188 number of viral genome copies in culture supernatants when treated with concentrations >20 µg/ml 189 and fully blocked EAV replication at 50 µg/ml ( Figure 4B and 4C) .