Sodium valproate-induced potentiation of antiherpetic effect of acyclovir

ABSTRACT

Sodium valproate [VPA], an anticonvalsant drug, has been reported to stimulate viral replication. A combination therapy with VPA and acyclovir [ACV] is used for the treatment of herpesvirus encephalitis, the commonest sporadic encephalitis of viral origin. To determine a possible interaction between VPA and ACV leading to a modification of antiviral activity of ACV. Cultured Hela cells were treated with 5 micro M of ACV and various concentrations of VPA followed by infection with herpes simplex virus type 1 [HSV-1]. Virus replication was monitored by quantal assay. Further investigations comprised electron microscopy, immunoperoxidase and immunoblot procedures. Possible chemical interaction between VPA and ACV was studied by nuclear magnetic resonance [NMR] spectrometer. Combined treatment of infected cells with ACV and VPA revealed 50- to 250-fold potentiation of antiviral activity of ACV by increasing VPA concentrations. Examination by NMR spectrometer showed a strong chemical interaction between amino groups of ACV and carboxyl part of VPA. The present in vitro studies should be paralleled by appropriate in vivo investigations, and if substantiated, a combination therapy with ACV and VPA may supersede single ACV therapy for herpesvirus encephalitis. Further studies are thus needed to establish which of VPA metabolites or newly-formed compounds is accountable for augmentation of antiviral effect of ACV