Potentiation of the anti-HIV activity of zalcitabine and lamivudine by a CTP synthase inhibitor, 3-deazauridine.
Low levels of the CTP synthase inhibitor 3-deazauridine (3-DU) strongly potentiated the anti-HIV-1 activity of the 5'-triphosphates of the cytidine-based analogues [-]2'-deoxy-3'-thiacytidine (3TC; lamivudine) and 2',3'-dideoxycytidine (ddC). The potentiation was associated with a 3-DU-induced decrease in dCTP pool size; no changes were seen in cellular pool sizes of dATP, dGTP or dTTP.
Gao
W Y
WY
Experimental Retrovirology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA.
Johns
D G
DG
Mitsuya
H
H
D015092:3-Deazauridine / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000494:pharmacology*; D019731:Carbon-Nitrogen Ligases / Q000037:antagonists & inhibitors*; D003842:Deoxycytidine Kinase / Q000378:metabolism; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D019259:Lamivudine / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects; D016047:Zalcitabine / Q000494:pharmacology*
D019380:Anti-HIV Agents; D004791:Enzyme Inhibitors; D018894:Reverse Transcriptase Inhibitors; D015092:3-Deazauridine; D019259:Lamivudine; D016047:Zalcitabine; D003842:Deoxycytidine Kinase; D019731:Carbon-Nitrogen Ligases; C019951:CTP synthetase