Enhancing the Antiviral Efficacy of RNA-Dependent RNA Polymerase Inhibition by Combination with Modulators of Pyrimidine Metabolism

Qi Liu; Amita Gupta; Ayse Okesli-Armlovich; Wenjie Qiao; Curt R. Fischer; Mark Smith; Jan E. Carette; Michael C. Bassik; Chaitan Khosla

. CC-BY-NC 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.24.992230 doi: bioRxiv preprint Nucleoside Synthesis. Antimicrob. Agents Chemother. 59, 2086-2093. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.24.992230 doi: bioRxiv preprint Figure S4 : Analysis of intracellular pyrimidine pools in A549 cells upon drug addition. (A) LC-MS analysis of intracellular pyrimidine TP, DP and MP pools after 6 h indicated drug treatment. Row 1 data is repeated from Figure 4A. (B) LC-MS analysis of intracellular pyrimidine TP, DP and MP pools after 12 h indicated drug treatment. In all assays, cell culture medium was supplemented with 5 µM uridine and 1 µM GSK983. Dipyridamole (DPY)-a nucleoside transport inhibitor-was used as . CC-BY-NC 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.24.992230 doi: bioRxiv preprint a positive control. Bars indicate means ± S.D, n = 3 and dots represent individual values. The statistical significance of comparisons to the untreated controls are indicated for uridine compounds (blue) and cytidine compounds (red) with * (p<0.05), ** (p<0.01), *** (p<0.001) or n.s. (p>0.05) using one-way ANOVA, Dunnett's test. In the DP graphs, the red line indicates the lower limit of reliable linear quantitation for CDP. Statistical tests were not carried out for CDP as many samples fell below the LLOQ. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.24.992230 doi: bioRxiv preprint The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.24.992230 doi: bioRxiv preprint The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.24.992230 doi: bioRxiv preprint . CC-BY-NC 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.24.992230 doi: bioRxiv preprint