Mechanisms of Antiretroviral Compounds in Inhibition of Viral and Cellular DNA Polymerases

Abstract

Many antiretroviral agents have been designed to target the reverse transcriptase molecule. Most if not all ot these compounds have, however, some degree of in vitro cytotoxicity and/or in vivo side effects. Selectivity of an antiviral compound depends, at least in part, on its enzyme specificity for inhibition (i.e., different effectiveness for reverse transcriptase and host cell DNA polymerases). The inhibitory effects of various compounds, thus far proven to suppress reverse transcriptase, on the cellular DNA polymerases α, β and γ were examined. Many of these reverse transcriptase inhibitors were found to be more or less inhibitory to the host cell DNA polymerases as well. The results obtained by parallel testing of antiretroviral agents for the inhibition of eukaryotic DNA polymerases provide useful information about the selectivity of the compounds. Such findings also foster the modification of drug structures for improvement of the efficacies of antiviral potentials.