INHIBITION OF EPISOMAL HEPATITIS-B VIRUS-DNA IN-VITRO BY -7-(2-DEOXY-2-FLUORO-BETA-D-ABINOFURANOSYL)PYRROLO [2,3-D]PYRIMIDINE

The nucleoside analog o-beta-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidi ne (T70080) and several related compounds were evaluated for anti-hepa titis B virus (HBV) activity by using cultured 2.2.15 cells. T70080 re duced episomal viral replication in these cells by 50% at a concentrat ion of 0.7 mu g/ml. At the same time, T70080 reduced cellular prolifer ation by 50% at a concentration in excess of 100 mu g/ml, yielding a t herapeutic index of > 143. In cells cultured for 12 days in the presen ce of 10 or 50 mu g of T70080 per mi and then with drug-free medium, f or an additional 12 days, viral DNA replication was completely inhibit ed initially but resumed between 6 and 12 days post-drug removal. In v iew of the potent anti-HBV activity shown, T70080 is a good candidate for further evaluation as a treatment of human HBV infection.