Author: Qi Liu; Amita Gupta; Ayse Okesli-Armlovich; Wenjie Qiao; Curt R. Fischer; Mark Smith; Jan E. Carette; Michael C. Bassik; Chaitan Khosla
Title: Enhancing the Antiviral Efficacy of RNA-Dependent RNA Polymerase Inhibition by Combination with Modulators of Pyrimidine Metabolism Document date: 2020_3_25
ID: 1zk64gsg_32
Snippet: Synthesis and evaluation of a series of CPU analogs revealed that CPU and 5-F-CPU were substrates of UCK2, and the resulting monophosphates were substrates of CMPK1. In combination with GSK983, the flux of CPU and 5-F-CPU to their triphosphate forms depleted intracellular pools of pyrimidine NTPs ( Figure 4A ). As the non-substrate analogue 5'-F-CPU did not deplete intracellular pyrimidines despite in vitro UCK2 inhibitory activity, our results s.....
Document: Synthesis and evaluation of a series of CPU analogs revealed that CPU and 5-F-CPU were substrates of UCK2, and the resulting monophosphates were substrates of CMPK1. In combination with GSK983, the flux of CPU and 5-F-CPU to their triphosphate forms depleted intracellular pools of pyrimidine NTPs ( Figure 4A ). As the non-substrate analogue 5'-F-CPU did not deplete intracellular pyrimidines despite in vitro UCK2 inhibitory activity, our results suggest that CPU's activity in host cells is driven by its ability to block multiple targets in pyrimidine salvage rather than solely UCK2 inhibition.
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