Potentiation of The Anti-HIV Activity of Zalcitabine and Lamivudine by a CTP Synthase Inhibitor, 3-Deazauridine

Abstract

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.