Selected article for: "nucleoside triphosphate form and triphosphate form"

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_24
    Snippet: Given that the CPU-GSK983 combination was able to selectively inhibit viral infection through modulation of intracellular nucleotide pools, we hypothesized that the combination should potentiate the effects of an RdRp inhibitor on viral genome replication. Among RdRp inhibitors, the nucleoside inhibitor (NI) class is the largest (Klumpp et al., 2006) and has progressed the furthest in studies against dengue virus (Lim et al., 2015) . Many NIs are.....
    Document: Given that the CPU-GSK983 combination was able to selectively inhibit viral infection through modulation of intracellular nucleotide pools, we hypothesized that the combination should potentiate the effects of an RdRp inhibitor on viral genome replication. Among RdRp inhibitors, the nucleoside inhibitor (NI) class is the largest (Klumpp et al., 2006) and has progressed the furthest in studies against dengue virus (Lim et al., 2015) . Many NIs are nucleoside analogs that rely on intracellular phosphorylation to form triphosphate substrates that block RdRp (Sofia et al., 2012) . For example, the cytidine analogue 4'-azidocytidine (R1479) and its prodrug balapiravir (R1626) have been assessed for treating HCV, and later dengue virus infections (Chen et al., 2014; Klumpp et al., 2006) . However, balapiravir failed in clinical trials against dengue due to limited efficacy (Nguyen et al., 2013) .

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