The ribonucleotide reductase inhibitor (E)-2'-fluoromethylene-2'-deoxycytidine (MDL 101,731): a potential topical therapy for herpes simplex virus infection.

The ribonucleotide reductase inhibitor MDL 101,731 was examined for antiviral activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in vitro and in combination with acyclovir in the murine zosteriform model of HSV-1 infection. The in vitro antiviral activity (IC50) for both serotypes of HSV was similar and in the range 23-98 nM for Vero cells. Comparable activities were obtained against acyclovir-resistant viruses. In the zosteriform model, topical combination therapy of MDL 101,731 with acyclovir (5%:5% w/w) applied 48 h after infection was more effective than acyclovir alone and even appeared to promote lesion resolution.