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10.1016/j.chembiol.2020.05.002 http://scihub22266oqcxt.onion/10.1016/j.chembiol.2020.05.002 32442424!7241336!32442424     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=32442424&cmd=llinks): Failed to open stream: HTTP request failed! 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Enhancing the Antiviral Efficacy of RNA-Dependent RNA Polymerase Inhibition by Combination with Modulators of Pyrimidine Metabolism |pdf=|usr=}}{{32442424}} gab.com Text Enhancing the Antiviral Efficacy of RNA-Dependent RNA Polymerase Inhibition by Combination with Modulators of Pyrimidine Metabolism JO: Cell Chem Biol http://www.kidney.de/pget.php?&tw=1&pmid=32442424 #FOAvip Genome-wide analysis of the mode of action of GSK983, a potent antiviral agent, led to the identification of dihydroorotate dehydrogenase as its target along with the discovery that genetic knockdown of pyrimidine salvage sensitized cells to GSK983. Because GSK983 is an ineffective antiviral in the presence of physiological uridine concentrations, we explored combining GSK983 with pyrimidine salvage inhibitors. We synthesized and evaluated analogs of cyclopentenyl uracil (CPU), an inhibitor of uridine salvage. We found that CPU was converted into its triphosphate in cells. When combined with GSK983, CPU resulted in large drops in cellular UTP and CTP pools. Consequently, CPU-GSK983 suppressed dengue virus replication in the presence of physiological concentrations of uridine. In addition, the CPU-GSK983 combination markedly enhanced the effect of RNA-dependent RNA polymerase (RdRp) inhibition on viral infection. Our findings highlight a new host-targeting strategy for potentiating the antiviral activity of RdRp inhibitors. Twit Text FOAVip Enhancing the Antiviral Efficacy of RNA-Dependent RNA Polymerase Inhibition by Combination with Modulators of Pyrimidine Metabolism ????Cell Chem Biol http://www.kidney.de/pget.php?&tw=1&pmid=32442424 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32442424 #FOAvip English Wikipedia <ref>{{Cite pmid|32442424}}</ref> Enhancing the Antiviral Efficacy of RNA-Dependent RNA Polymerase Inhibition by Combination with Modulators of Pyrimidine Metabolism #MMPMID32442424 Liu Q; Gupta A; Okesli-Armlovich A; Qiao W; Fischer CR; Smith M; Carette JE; Bassik MC; Khosla C Cell Chem Biol 2020[Jun]; 27 (6): 668-677.e9 PMID32442424show ga Genome-wide analysis of the mode of action of GSK983, a potent antiviral agent, led to the identification of dihydroorotate dehydrogenase as its target along with the discovery that genetic knockdown of pyrimidine salvage sensitized cells to GSK983. Because GSK983 is an ineffective antiviral in the presence of physiological uridine concentrations, we explored combining GSK983 with pyrimidine salvage inhibitors. We synthesized and evaluated analogs of cyclopentenyl uracil (CPU), an inhibitor of uridine salvage. We found that CPU was converted into its triphosphate in cells. When combined with GSK983, CPU resulted in large drops in cellular UTP and CTP pools. Consequently, CPU-GSK983 suppressed dengue virus replication in the presence of physiological concentrations of uridine. In addition, the CPU-GSK983 combination markedly enhanced the effect of RNA-dependent RNA polymerase (RdRp) inhibition on viral infection. Our findings highlight a new host-targeting strategy for potentiating the antiviral activity of RdRp inhibitors. |Animals[MESH] |Antiviral Agents/chemistry/metabolism/*pharmacology[MESH] |Carbazoles/chemistry/metabolism/pharmacology[MESH] |Cells, Cultured[MESH] |Chlorocebus aethiops[MESH] |Dengue Virus/*drug effects[MESH] |Enzyme Inhibitors/chemistry/metabolism/*pharmacology[MESH] |Female[MESH] |Humans[MESH] |Male[MESH] |Microbial Sensitivity Tests[MESH] |Molecular Structure[MESH] |Pyrimidines/*antagonists & inhibitors/metabolism[MESH] |RNA-Dependent RNA Polymerase/*antagonists & inhibitors/metabolism[MESH] |Uridine/analogs & derivatives/metabolism/*pharmacology[MESH]Enhancing the Antiviral Efficacy of RNA-Dependent RNA Polymerase Inhib(epmc).pdf DeepDyve Pubget Overpricing