Author/Authors :
Moattari, A Department of Bacteriology and Virology, Shiraz University of Medical Sciences - Department of Virology Iran University of Medical Sciences - School of Veterinary Medicine and Department of Chemistry Shiraz University , Kabiri, M Department of Bacteriology and Virology, Shiraz University of Medical Sciences - Department of Virology Iran University of Medical Sciences - School of Veterinary Medicine and Department of Chemistry Shiraz University , Shahrabadi, MS Department of Bacteriology and Virology, Shiraz University of Medical Sciences - Department of Virology Iran University of Medical Sciences - School of Veterinary Medicine and Department of Chemistry Shiraz University , Akbari, S Department of Bacteriology and Virology, Shiraz University of Medical Sciences - Department of Virology Iran University of Medical Sciences - School of Veterinary Medicine and Department of Chemistry Shiraz University , Iranpoor, N Department of Bacteriology and Virology, Shiraz University of Medical Sciences - Department of Virology Iran University of Medical Sciences - School of Veterinary Medicine and Department of Chemistry Shiraz University , Motamedifar, M Department of Bacteriology and Virology, Shiraz University of Medical Sciences - Department of Virology Iran University of Medical Sciences - School of Veterinary Medicine and Department of Chemistry Shiraz University
Abstract :
Background: 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.
Objective: To determine a possible interaction between VPA and
ACV leading to a modification of antiviral activity of ACV.
Methods: Cultured Hela cells were treated with 5mM 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.
Results: 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.
Conclusion: 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
Keywords :
Sodium valproate , acyclovir , nuclear magnetic resonance , immunopeoxidase , HSV-1
