Synergistic Antiviral Activity of Acyclovir and Vidarabine Against Herpes Simplex Virus Types 1 and 2 and Varicella-Zoster Virus

Antiviral Res. 2006 Nov;72(2):157-61. doi: 10.1016/j.antiviral.2006.05.001. Epub 2006 May 30.

Abstract

Acyclovir and vidarabine both exhibit anti-herpetic activity. Because different mechanisms of action of vidarabine and acyclovir have been reported, we analyzed their combined anti-herpetic activity on plaque formation of herpes simplex virus (HSV)-1, HSV-2, and varicella-zoster virus (VZV) by isobolograms. The results indicate that acyclovir and vidarabine have a synergistic effect on wild type HSV-1, HSV-2, and VZV. The susceptibility of thymidine kinase-deficient HSV-1 to vidarabine was not affected by the presence of acyclovir, suggesting that phosphorylation of acyclovir is essential for synergism. The combined anti-HSV activity of acyclovir and vidarabine against phosphonoacetic acid-resistant HSV-1 with DNA polymerase mutation did not show synergism in contrast to that against wild-type herpesviruses. Alteration of the substrate specificity of viral DNA polymerase to acyclovir and vidarabine annihilated the synergism. Thus, the nature of their binding sites on DNA polymerase is important to the synergistic anti-herpesvirus activity of acyclovir and vidarabine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclovir / pharmacology*
  • Antiviral Agents / pharmacology*
  • Cell Line
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism
  • Drug Resistance, Viral
  • Drug Synergism
  • Gene Deletion
  • Herpesvirus 1, Human / drug effects*
  • Herpesvirus 2, Human / drug effects*
  • Herpesvirus 3, Human / drug effects*
  • Humans
  • Phosphonoacetic Acid / pharmacology
  • Phosphorylation
  • Thymidine Kinase / genetics
  • Thymidine Kinase / metabolism
  • Vidarabine / pharmacology*
  • Viral Plaque Assay
  • Viral Proteins / genetics
  • Viral Proteins / metabolism

Substances

  • Antiviral Agents
  • Viral Proteins
  • Thymidine Kinase
  • DNA-Directed DNA Polymerase
  • Vidarabine
  • Phosphonoacetic Acid
  • Acyclovir