ANTI-(HUMAN IMMUNODEFICIENCY VIRUS) ACTIVITY OF POLYOXOTUNGSTATES ANDTHEIR INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS REVERSE-TRANSCRIPTASE

Heteropolyoxotungstates of the Keggin class containing different heter oatoms were tested for inhibition of two strains of human immunodefici ency virus 1 (HIV-1); they exhibited varying antiviral activity. Compo unds containing boron were inactive, only one of those containing phos phorus showed selective anti-viral activity, whereas all silicon-conta ining compounds exhibited significant anti-viral activity in C8166 cel ls infected with the IIIB strain. Their effectiveness was some 10-fold higher in JM cells with selectivity indices of about 2000. The silico tungstates were effective inhibitors of HIV reverse transcriptase, sho wing greater inhibition with RNA/DNA template primers than with DNA/DN A template . primer. Kinetic analysis demonstrated that they inhibit t he enzyme by different mechanisms, as, of the four compounds examined, two competed with template . primer and two competed with deoxynucleo side triphosphate. Inhibition of DNA polymerase activity by these comp ounds was compared using polymerases from different sources, including human; although not necessarily most specific for HIV-1 reverse trans criptase, they did not inhibit all DNA polymerases to a similar degree .