IN-VITRO ANTIVIRAL ACTIVITY OF PENCICLOVIR, A NOVEL PURINE NUCLEOSIDE, AGAINST DUCK HEPATITIS-B VIRUS

The in vitro antihepadnavirus activities of the purine nucleoside anal ogs ganciclovir -[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine} and penciclovir [9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine; BRL 391231 were compared in primary duck hepatocyte cultures congenitally infect ed with the duck hepatitis B virus (DHBV). Both compounds inhibited DH BV DNA replication to a comparable extent during continuous short-term treatment of the cultures. However penciclovir was more active both d uring longer-term continuous treatment (50% inhibitory concentrations: penciclovir, 0.7 +/- 0.1 muM; ganciclovir, 4.0 +/- 0.2 muM) and in wa shout experiments (50% inhibitory concentrations: penciclovir, 3.0 +/- 0.4 muM; ganciclovir, 46 +/- 1.5 muM) designed to compare the persist ence of inhibitory activity after removal of the extracellular compoun d. The effects on viral protein synthesis were similar to the effects on viral DNA replication. These data suggest that penciclovir or its o ral form, famciclovir, may have clinical utility in the treatment of c hronic hepatitis B virus infection.