Synergistic antiviral activity of acyclovir and vidarabine against herpes simplex virus types 1 and 2 and varicella-zoster virus

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• 作者：Mikiko Suzuki ; Tomoko Okuda and Kimiyasu Shiraki
• 关键词：Herpes simplex viruses ; Varicella-zoster virus ; Drug interactions ; Synergism ; Acyclovir ; Vidarabine
• 刊名：Antiviral Research
• 出版年：2006
• 出版时间：November 2006
• 年：2006
• 卷：72
• 期：2
• 页码：157-161
• 全文大小：228 K

文摘

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.