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
Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
Antiviral Res. 2008 Jul;79(1):62-70. doi: 10.1016/j.antiviral.2008.01.156. Epub 2008 Feb 21.
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 (EC(50)) of 0.05 microM. The 50% cytotoxicity concentration (CC(50)) of digitoxin is 10.66 microM 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.
单纯疱疹病毒1型（HSV-1）可在神经系统中建立潜伏感染，在免疫功能低下的个体中重新激活时通常会导致危及生命的疾病。在大多数情况下，使用传统核苷类似物如阿昔洛韦进行治疗是有效的，但由于免疫功能低下个体的长期治疗，可能会产生耐药性。在本研究中，我们鉴定出一种正在使用的药物洋地黄毒苷，它能有效抑制HSV-1复制，50%有效浓度（EC50）为0.05微摩尔。洋地黄毒苷的50%细胞毒性浓度（CC50）为10.66微摩尔，由此得出的选择性指数为213。洋地黄毒苷的几种结构类似物，如地高辛、八水合哇巴因和毒毛花苷G也显示出抗HSV活性。洋地黄毒苷的抑制作用可能在HSV-1复制的早期阶段和病毒释放阶段发挥作用。洋地黄毒苷能抑制阿昔洛韦耐药病毒这一观察结果进一步表明，洋地黄毒苷代表了一类新型药物，其抗病毒机制与传统药物不同。
