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

Kanizsai, Szilvia and Ghidán, Ágoston and Ongrádi, Joseph and Nagy, Károly (2012) Antiretroviral effect of 4-thio-uridylate against human immunodeficiency virus type 1. Acta Microbiologica et Immunologica Hungarica, 59 (4). pp. 499-510. ISSN 1217-8950

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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-1IIIB with IC50 values of 11.7 μg/ml. In a single-cycle viral infection assay (MAGI assay) UD29 proved to have a potent inhibitory effect against HIV-1IIIB on HeLaCD4-LTR/β-gal cells, which was dose dependent with IC50 values of 4.75 μg/ml and IC90 of 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.

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