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

We were also interested in exploring the antiviral capacity of two new BSA, IPPA17-04 and GAC50 163 that impair viral replication through inhibition of de novo pyrimidine biosynthesis in host cells. Using 164 our in vitro EAV infection assay, we tested first the cytotoxicity of both compounds. IPPA17-A04 and 165 GAC-50 treatment did not show any sign of cytotoxicity on ED cells. At 100 µg/ml, cell viability was 166 above 80% after 48h of treatment, but cytostatic effects were observed as expected for this class of 167 drug ( Figure 2B and 2C). These results indicate that TC 50 for IPPA17-A04 and GAC-50 is over 100 168 µg/ml in ED cells. We then explored the cytoprotective effect of these two compounds in EAV-infected 169 cultures at different concentrations. Our results showed that after 48 h of culture, the viability of 170 infected ED cells reached 79% when treated with 1 µg/ml of IPPA17-A04, and was above 80% when 171 treated with concentrations >5 µg/ml ( Figure 3B ). The IC 50 of IPPA17-A04 was estimated at 0.70 172 µg/ml, i.e. 1.74 µM. GAC50 is not as effective since viability of ED infected cells treated with GAC50 is 173 >80% only at the highest concentrations of 20 or 50 µg/ml ( Figure 3C ) with an IC 50 at 7.2 µg/ml, i.e. 174 author/funder. All rights reserved. No reuse allowed without permission.