Cheung Yan Yi, Chen Karen Caiyun, Chen Huixin, Seng Eng Khuan, Chu Justin Jang Hann
Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System, 5 Science Drive 2, National University of Singapore, Singapore 117597, Singapore.
School of Chemical & Life Sciences, 180 Ang Mo Kio Ave 8, Nanyang Polytechnic, Singapore 569830, Singapore.
Antiviral Res. 2014 Nov;111:93-9. doi: 10.1016/j.antiviral.2014.09.007. Epub 2014 Sep 22.
Dengue infection poses a serious threat globally due to its recent rapid spread and rise in incidence. Currently, there is no approved vaccine or effective antiviral drug for dengue virus infection. In response to the urgent need for the development of an effective antiviral for dengue virus, the US Drug Collection library was screened in this study to identify compounds with anti-dengue activities. Lanatoside C, an FDA approved cardiac glycoside was identified as a candidate anti-dengue compound. Our data revealed that lanatoside C has an IC50 of 0.19μM for dengue virus infection in HuH-7 cells. Dose-dependent reduction in dengue viral RNA and viral proteins synthesis were also observed upon treatment with increasing concentrations of lanatoside C. Time of addition study indicated that lanatoside C inhibits the early processes of the dengue virus replication cycle. Furthermore, lanatoside C can effectively inhibit all four serotypes of dengue virus, flavivirus Kunjin, alphavirus Chikungunya and Sindbis virus as well as the human enterovirus 71. These findings suggest that lanatoside C possesses broad spectrum antiviral activity against several groups of positive-sense RNA viruses.
登革热感染由于其近期的迅速传播和发病率上升，在全球构成了严重威胁。目前，尚无针对登革热病毒感染的获批疫苗或有效抗病毒药物。为了应对开发登革热病毒有效抗病毒药物的迫切需求，本研究对美国药物收集库进行了筛选，以鉴定具有抗登革热活性的化合物。毛花苷C，一种FDA批准的强心苷，被鉴定为候选抗登革热化合物。我们的数据显示，毛花苷C在HuH-7细胞中对登革热病毒感染的IC50为0.19μM。在用浓度不断增加的毛花苷C处理后，还观察到登革热病毒RNA和病毒蛋白合成呈剂量依赖性减少。添加时间研究表明，毛花苷C抑制登革热病毒复制周期的早期过程。此外，毛花苷C可有效抑制登革热病毒的所有四种血清型、库京病毒、基孔肯雅病毒和辛德毕斯病毒以及人肠道病毒71型。这些发现表明，毛花苷C对几类正链RNA病毒具有广谱抗病毒活性。
