Inhibition of herpes simplex virus DNA replication by ara-tubercidin

Preliminary studies of the biochemical basis for the antiviral activity of the pyrrolo[2,3- d]pyrimidine nucleoside ara-tubercidin were conducted. Herpes simplex virus DNA synthesis was 3-fold more sensitive to inhibition by ara-tubercidin than was cellular DNA synthesis. Partially purified herpes DNA polymerases were more sensitive to inhibition by ara-tubercidin 5′-triphosphate than were cellular polymerases α and β. Inhibition of viral DNA polymerase was competitive with dATP and noncompetitive with dTTP. The results suggest that the viral DNA polymerase plays a significant role in the antiviral activity of ara-tubercidin.