Enhancement of antiherpetic activity of cytarabine by hydroxyurea in humanembryonic skin-muscle fibroblasts

Pharmocological induction of low deoxyribonucleoside triphosphate (dNTP) le vels is a novel approach to combine inhibition of virus replication. In acc ordance with this concept, the alteration of antiherpes activity of cytarab ine (AraC) in combination with hydroxyurea (HU), an inhibitor of ribonucleo tide reductase, was studied. The results were confirmed by virus yield assa ys in human embryonic skin-muscle fibroblasts (HESMF). It was demonstrated that HU significantly enhanced the antiviral activity of AraC against HSV-1 and HSV-2 in HESMF cultures and this inhibition was reversed by an excess of deoxycytidine (dCyt). The observations suggest that the reduction in dCT P level accounts for the potentiating effect of HU on the antiviral activit y of AraC.