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Antiviral activity of ganciclovir elaidic acid ester against herpesviruses.

Abstract：

:A fatty acid derivative of ganciclovir (GCV), elaidic acid ganciclovir (E-GCV), has been evaluated for its inhibitory activity against laboratory and clinical strains of herpes simplex type 1 (HSV-1) and type 2 (HSV-2), varicella-zoster virus (VZV) and human cytomegalovirus (HCMV) in human embryonic lung fibroblasts. GCV, cidofovir, acyclovir (ACV), brivudin (BVDU) and foscarnet (PFA) were included as reference compounds. The viruses studied were wild-type, thymidine kinase-deficient (TK(-)) and PFA-resistant (PFA(r)) HSV strains. The IC(50) values obtained for E-GCV were 5- to 30-fold lower than those observed for GCV, the IC(50) value of E-GCV for HSV-1 strain KOS being 0.07 nM. A similarly increased activity of E-GCV (as compared to GCV) was noted 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-GCV, 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 than GCV in terms of reduction of mortality rate and delay of mean time of death. The elaidic acid ester of GCV should therefore be considered as a novel approach towards the treatment of HSV infections.

journal_name

Antiviral Res

journal_title

Antiviral research

authors

Andrei G,Snoeck R,Neyts J,Sandvold ML,Myhren F,De Clercq E

doi

10.1016/s0166-3542(00)00070-x

subject

Has Abstract

pub_date

2000-03-01 00:00:00

pages

157-67

issue

3

eissn

0166-3542

issn

1872-9096

pii

S016635420000070X

journal_volume

45

pub_type

杂志文章

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