Antiretroviral effect of 4-thio-uridylate against human immunodeficiency virus type 1

Abstract

Antiretroviral effect of thiolated nucleotide 4-thio-uridylate (S4UMP, designated as UD29) against human immunodeficiency virus type 1 (HIV-1) have been quantitatively determined in cell-based viral infectivity assays. In syntitium inhibition assay on MT-2 human T-cell line UD29 prevented cell fusion and formation of syntitia induced by HIV-1IIIBwith IC50values of 11.7 μg/ml. In a single-cycle viral infection assay (MAGI assay) UD29 proved to have a potent inhibitory effect against HIV-1IIIBon HeLaCD4-LTR/β-gal cells, which was dose dependent with IC50values of 4.75 μg/ml and IC90of 39.7 μg/ml. UD29 showed a most prominent antiviral effect when administered 30 min prior HIV-1 infection. As HIV entry requires thiol/disulfide exchange process, results suggest that reactive -SH group of enol-form of the thiolated nucleotide may interfere with the function of cell surface proteins. UD29 cannot penetrate into cells and may have an interactive role in redox processes active in viral entry.