Fig. 6.

Atovaquone does not target pyrimidine synthesis pathway Vero E6 cells at 1 and 5 µM. (A) Metabolomic analyses for of Vero E6 cells treated with DMSO or Atovaquone, at, showing no change in the uridine monophosphate (UMP) levels at 1 and 5 µM, and significant depletion in UMP levels at 10 µM. (B) Molecular pathway of de novo pyrimidine synthesis. (C) Levels of UMP with respect to orotate and dihydroorotate levels in Vero E6 cells treated with 1, 5, and 10 µM atovaquone, showing only depletion in the UMP levels at 10 µM ATO. (D)SARS-CoV-2 replication in the presence of 5 µM and 100 µM uridine treated with 1.5, 5, and 10 µM atovaquone or 5 µM vidofludimus (potent DHODH inhibitor). Atovaquone showed significant inhibition for viral replication regardless the uridine concentration, however vidofludimus activity changed based on the uridine addition. Data represent average of biological triplicates. Error bars, SEM.