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

The half maximal toxic concentration (TC 50 ), which is the concentration that kills 50% of the cells in 154 culture, was estimated to be >100 µg/ml for ribavirin. Then, we tested the effect of ribavirin in our in 155 vitro EAV infection model at the non-cytotoxic concentration range of 0.5 to 20 µg/ml. As shown in 156 Figure 3A , ATP quantification in infected culture wells at 48 h showed that only 35% of cells were alive 157 in the absence of ribavirin as opposed to 67% in presence of the drug at 0.5 µg/ml. The viability of 158 infected cells was above 80% when treated with ribavirin at 2, 5 or 10 µg/ml ( Figure 3A ). These results 159 were used to calculate the half maximal inhibitory concentration (IC 50 ) of ribavirin that was estimated 160 to 0.90 µg/ml, i.e. 3.7 µM. This demonstrates that ribavirin is able to protect ED cells against EAV-161 associated cytopathic effects. 162