Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and human herpesvirus 8 (HHV-8) are responsible for a number of clinical manifestations in both normal and immunocompromised individuals. The parent
benzimidazole ribonucleosides evaluated in this series, 2-bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)benzimidazole (BDCRB) and
maribavir (
1263W94), are potent and selective inhibitors of human CMV replication. These
nucleosides act by two different mechanisms. BDCRB blocks the processing and maturation of
viral DNA, whereas
1263W94 inhibits the viral
enzyme pUL97 and interferes with
DNA synthesis. In the present study, we have evaluated the in vitro
antiviral activity of BDCRB, an analog,
GW275175X (175X), and
1263W94 against the replication of HSV-1, HSV-2, VZV, CMV, EBV, HHV-6, and HHV-8. By using various methodologies, significant activity was observed against human CMV and EBV but not against HSV-1, HSV-2, VZV, HHV-6, or HHV-8. Plaque reduction assays performed on a variety of laboratory and clinical isolates of human CMV indicated that all strains, including those resistant to
ganciclovir (GCV) and
foscarnet, were sensitive to all three
benzimidazole ribonucleosides, with mean 50% effective concentration values of about 1 to 5 microM compared to that of GCV at 6 microM. The toxicity of these compounds in tissue culture cells appeared to be similar to that observed with GCV. These results demonstrate that the
benzimidazole ribonucleosides are active against human CMV and EBV and suggest that they may be useful for the treatment of
infections caused by these herpesviruses.