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.
Bridges
C G
CG
Marion Merrell Dow Research Institute Laboratories, MRC Collaborative Centre, London, UK.
Ahmed
S P
SP
Sunkara
P S
PS
McCarthy
J R
JR
Tyms
A S
AS
D000212:Acyclovir / Q000494:pharmacology; D000287:Administration, Topical; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006561:Herpes Simplex / Q000188:drug therapy* / Q000473:pathology; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D003841:Deoxycytidine; D012264:Ribonucleotide Reductases; C086432:tezacitabine; D000212:Acyclovir