Honokiol, a Lignan Biphenol Derived from the Magnolia Tree, Inhibits Dengue Virus Type 2 Infection.
Honokiol, a Lignan Biphenol Derived from the Magnolia Tree, Inhibits Dengue Virus Type 2 Infection.
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DOI：
10.3390/v7092852
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发表时间：
2015-09-10
期刊：
影响因子：
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通讯作者：
Huang KJ
中科院分区：
文献类型：
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作者：
Fang CY;Chen SJ;Wu HN;Ping YH;Lin CY;Shiuan D;Chen CL;Lee YR;Huang KJ
登革热是最广泛的虫媒病毒感染，在热带和亚热带国家构成严重的健康和经济问题。目前没有许可的疫苗或化合物可用于预防或控制登革热病毒（DENV）感染的严重性。檀香木是一种从木兰树中提取的木酚素，通常用于东方医学。在这里，我们报告了和诺平对血清2型DENV（DENV-2）具有深刻的抗病毒活性。除了抑制细胞内DENV-2复制子之外，和诺明还显示出抑制DENV-2在幼仓鼠肾（BHK）和人肝癌Huh 7细胞中的复制。在最大无毒剂量的和厚朴处理下，BHK和Huh 7细胞中感染性DENV颗粒的产生减少>90%。潜在的机制揭示了DENV-2非结构蛋白NS 1/NS 3及其复制中间体双链RNA的表达通过和诺酮治疗显著降低。和厚朴对DENV推定受体的表达没有影响，但可能通过消除DENV包膜糖蛋白和早期内体的共定位来干扰DENV-2的内吞作用。这些结果表明，和厚朴酚抑制DENV-2的复制、病毒基因表达和内吞过程，使其成为用于DENV感染的化疗的有希望的药剂。
Dengue is the most widespread arbovirus infection and poses a serious health and economic issue in tropical and subtropical countries. Currently no licensed vaccine or compounds can be used to prevent or manage the severity of dengue virus (DENV) infection. Honokiol, a lignan biphenol derived from the Magnolia tree, is commonly used in Eastern medicine. Here we report that honokiol has profound antiviral activity against serotype 2 DENV (DENV-2). In addition to inhibiting the intracellular DENV-2 replicon, honokiol was shown to suppress the replication of DENV-2 in baby hamster kidney (BHK) and human hepatocarcinoma Huh7 cells. At the maximum non-toxic dose of honokiol treatment, the production of infectious DENV particles was reduced >90% in BHK and Huh7 cells. The underlying mechanisms revealed that the expression of DENV-2 nonstructural protein NS1/NS3 and its replicating intermediate, double-strand RNA, was dramatically reduced by honokiol treatment. Honokiol has no effect on the expression of DENV putative receptors, but may interfere with the endocytosis of DENV-2 by abrogating the co-localization of DENV envelope glycoprotein and the early endosomes. These results indicate that honokiol inhibits the replication, viral gene expression, and endocytotic process of DENV-2, making it a promising agent for chemotherapy of DENV infection.