Inhibition of hepatitis B virus deoxyribonucleic acid polymerase by the 5'-triphosphates of 9-beta-D-arabinofuranosyladenine and 1-beta-D-arabinofuranosylcytosine

Abstract

9-beta-D-Arabinofuranosyladenine (ara-A), 1-beta-D-arabinofuranosylcytosine (ara-C), and their 5'-triphosphates (ara-ATP and ara-CTP) were tested for ability to inhibit the hepatitis B virus (HBV)-associated deoxyribonucleic acid (DNA) polymerase. Ara-C did not inhibit the HBV DNA polymerase at the concentrations tested, ara-A did so by 50% at a concentration of 30 mM, with the inhibition noncompetitive with respect to deoxyadenosine 5-triphosphate (dATP). Ara-ATP and ara-CTP inhibited the DNA polymerase test competitively with respect to dATP and dCTP, respectively. Both compounds were also active after initiation of the DNA polymerase reaction. The inhibition caused by ara-ATP and ara-CTP was shown to be reversible, with no evidence that ara-ATP or ara-CTP was incorporated into the HBV DNA.