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Anti-HSV activity of digitoxin and its possible mechanisms |
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| Authors: | Su Chun-Ting Hsu John T-A Hsieh Hsing-Pang Lin Pi-Han Chen Ting-Chi Kao Chuan-Liang Lee Chun-Nan Chang Sui-Yuan |
| Affiliation: | aDepartment of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan bDepartment of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan cDivision of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, Taiwan dDepartment of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan |
| Abstract: | Herpes simplex virus type 1 (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 μM. The 50% cytotoxicity concentration (CC50) of digitoxin is 10.66 μM 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. |
| Keywords: | Digitoxin HSV Cardiac glycoside |
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