Antiviral activity of lanatoside C against dengue virus infection

Antiviral activity of lanatoside C against dengue virus infection
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DOI:
10.1016/j.antiviral.2014.09.007
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发表时间:
2014-11-01
期刊:
影响因子:
7.6
通讯作者:
Chu, Justin Jang Hann
Chu, Justin Jang Hann
中科院分区:
医学2区
文献类型:
--
作者:
Cheung, Yan Yi;Chen, Karen Caiyun;Chu, Justin Jang Hann

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登革热感染由于其最近的快速传播和发病率上升而在全球构成严重威胁。目前,没有批准的疫苗或有效的抗病毒药物用于登革热病毒感染。针对开发有效的登革热病毒抗病毒药物的迫切需求,本研究从美国药物保藏中心文库中筛选具有抗登革热活性的化合物。毛花苷C是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细胞中对登革病毒感染的IC 50为0.19 μ M。在用增加浓度的毛花苷C处理后,还观察到登革病毒RNA和病毒蛋白合成的剂量依赖性减少。添加时间研究表明,毛花苷C抑制登革病毒复制周期的早期过程。此外,毛花苷C可以有效地抑制所有四种血清型的登革病毒、黄病毒昆津、甲病毒基孔肯雅和辛德毕斯病毒以及人肠道病毒71。这些结果表明,毛花苷C具有广谱抗几组正义RNA病毒的活性。(C)2014 Elsevier BM. All rights reserved.
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 0.19 mu M 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. (C) 2014 Elsevier BM. All rights reserved.