The synergistic effects of betulin with acyclovir against herpes simplex viruses

Yunhao Gong, Karim M. Raj, Carolyn A. Luscombe, Izabelle Gadawski, Teresa Tam, Jianhua Chu, David Gibson, Robert M Carlson, Stephen L. Sacks

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57 Scopus citations


Betulin, a pentacyclic triterpenoid, was isolated from the bark of Betula papyrifera. The antiviral efficacies of betulin on herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) were evaluated using viral plaque reduction assays on Vero cells. The results indicate that betulin is active against both HSV-1 and HSV-2 infections with the 50% effective concentrations (EC50) of 0.40 and 4.15 μg/ml, respectively. The cytotoxicity of betulin was examined on Vero cells using a neutral red uptake assay. The 50% cytotoxic concentration (CC50) of betulin was 73.1 μg/ml. A synergistic antiviral effect between betulin and acyclovir (ACV) was determined by drug combination studies. Strong and moderate synergistic antiviral effects were observed for betulin and ACV against HSV-1 when the concentrations of ACV and betulin were higher than 0.068 and 0.4 μg/ml, respectively. At the concentrations lower than these, additive effect was found. Synergistic antiviral effects were also found against HSV-2 at higher concentrations than for HSV-1, i.e. 0.45 μg/ml of ACV combined with 8.4 μg/ml of betulin.

Original languageEnglish (US)
Pages (from-to)127-130
Number of pages4
JournalAntiviral Research
Issue number2
StatePublished - Nov 2004

Bibliographical note

Copyright 2013 Elsevier B.V., All rights reserved.


  • Acyclovir.
  • Betulin
  • Drug combination
  • Herpes simplex viruses
  • Synergistic


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