ANTIVIRAL ACTION OF OLIGODEOXYGUANYLIC ACIDS AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

Deoxyguanylic acids, but not other deoxynucleotides, as short as 3- to 4-mer, were effective in preventing HIV-1-induced cytopathicity, In addition, they prevented giant cell formation of infected Sup-T1 cells, and p24 production in HIV-1 infected H9 cells, Phosphorylation at either the 5'- or 3'-end enhanced these activities, Furthermore, 5'-phosphorylated phosphorothioate tetradeoxyguanylic acid was effective in reducing HIV production in chronically infected cells (H9/IIIB). The search for the target steps of this compound revealed that it inhibits at least 3 steps in the life cycle of HIV: interaction with CD4 (measured by inhibitory effect on the syncytia formation between Sup-T1 and H9/IIIB cells), reverse transcriptase, and step(s) after integration, These results suggest that phosphorylated phosphorothioate tetradeoxyguanylic acid may be a novel candidate for a therapeutic agent of AIDS.