Antiviral activity of ganciclovir elaidic acid ester against herpesviruses

A fatty acid derivative of ganciclovir (GCV), elaidic acid ganciclovir (E-G CV), has been evaluated for its inhibitory activity against laboratory and clinical strains of herpes simplex type 1 (HSV-1) and type 2 (HSV-2), varic ella-zoster virus (VZV) and human cytomegalovirus (HCMV) in human embryonic lung fibroblasts. GCV, cidofovir, acyclovir (ACV), brivudin (BVDU) and fos carnet (PFA) were included as reference compounds. The viruses studied were wild-type, thymidine kinase-deficient (TK-) and PFA-resistant (PFA? HSV st rains. The IC50 values obtained for E-GCV were 5- to 30-fold lower than tho se observed for GCV, the IC50 value of E-GCV for HSV-I strain KOS being 0.0 7 nM. A similarly increased activity of E-GCV las compared to GCV) was note d for TK- and PFA(r) HSV-1 or HSV-2 strains. However, E-GCV did not exhibit superior activity over GCV to VZV or HCMV in vitro. The antiviral efficacy of E-GCV was also evaluated in vivo against intracerebral HSV-2 infection in NMRI mice. Animals were treated intraperitoneally or perorally with E-GC V, GCV or placebo once daily for 10 days, starting the day of infection. E- GCV compared to GCV at equimolar doses, proved markedly more efficacious th an GCV in terms of reduction of mortality rate and delay of mean time of de ath. The elaidic acid ester of GCV should therefore be considered as a nove l approach towards the treatment of HSV infections. (C) 2000 Elsevier Scien ce B.V. All rights reserved.