Journal
ANTIVIRAL RESEARCH
Volume 79, Issue 1, Pages 62-70Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.antiviral.2008.01.156
Keywords
digitoxin; HSV; cardiac glycoside
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Herpes simplex virus type I (HSV-1) can establish latent infection in the nervous system and usually leads to life-threatening diseases in immunocompromised individuals upon reactivation. Treatment with conventional nucleoside analogue such as acyclovir is effective in most cases, but drug-resistance may arise due to prolonged treatment in immunocompromised individuals. In this study, we identified an in-use medication, digitoxin, which actively inhibited HSV-1 replication with a 50% effective concentration (EC50) of 0.05 mu M. The 50% cytotoxicity concentration (CC50) of digitoxin is 10.66 mu M and the derived selective index is 213. Several structural analogues of digitoxin such as digoxin, ouabain octahydrate and G-strophanthin also showed anti-HSV activity. The inhibitory effects of digitoxin are likely to be introduced at the early stage of HSV-1 replication and the virus release stage. The observation that digitoxin can inhibit acyclovir-resistant viruses further implicates that digitoxin represents a novel drug class with distinct antiviral mechanisms from traditional drugs. (c) 2008 Elsevier B.V. All rights reserved.
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