Department of Virology, Paul-Ehrlich-Institut, 63225 Langen, Germany.
Pharmazeutische Chemie, Philipps-Universität Marburg, 35037 Marburg, Germany.
Viruses. 2018 Mar 27;10(4):149. doi: 10.3390/v10040149.
The Zika virus (ZIKV) outbreak in 2016 in South America with specific pathogenic outcomes highlighted the need for new antiviral substances with broad-spectrum activities to react quickly to unexpected outbreaks of emerging viral pathogens. Very recently, the natural compound silvestrol isolated from the plant was found to have very potent antiviral effects against the (-)-strand RNA-virus Ebola virus as well as against Corona- and Picornaviruses with a (+)-strand RNA-genome. This antiviral activity is based on the impaired translation of viral RNA by the inhibition of the DEAD-box RNA helicase eukaryotic initiation factor-4A (eIF4A) which is required to unwind structured 5´-untranslated regions (5'-UTRs) of several proto-oncogenes and thereby facilitate their translation. Zika virus is a flavivirus with a positive-stranded RNA-genome harboring a 5'-capped UTR with distinct secondary structure elements. Therefore, we investigated the effects of silvestrol on ZIKV replication in A549 cells and primary human hepatocytes. Two different ZIKV strains were used. In both infected A549 cells and primary human hepatocytes, silvestrol has the potential to exert a significant inhibition of ZIKV replication for both analyzed strains, even though the ancestor strain from Uganda is less sensitive to silvestrol. Our data might contribute to identify host factors involved in the control of ZIKV infection and help to develop antiviral concepts that can be used to treat a variety of viral infections without the risk of resistances because a host protein is targeted.
2016 年，南美洲爆发的 Zika 病毒（ZIKV）疫情，其特定的致病后果凸显了对具有广谱活性的新型抗病毒物质的需求，以便能够迅速应对新兴病毒病原体的意外爆发。最近，从植物中分离出的天然化合物 silvestrol 被发现对（-）链 RNA 病毒埃博拉病毒以及带有（+）链 RNA 基因组的 Corona 和 Picornaviruses 具有非常有效的抗病毒作用。这种抗病毒活性是基于通过抑制 DEAD-box RNA 解旋酶真核起始因子 4A（eIF4A）来削弱病毒 RNA 的翻译，该酶对于解开几个原癌基因的 5´-非翻译区（5'-UTR）并从而促进其翻译是必需的。Zika 病毒是一种带有正链 RNA 基因组的黄病毒，其 5´-UTR 带有独特的二级结构元件。因此，我们研究了 silvestrol 对 A549 细胞和原代人肝细胞中 ZIKV 复制的影响。使用了两种不同的 ZIKV 株。在感染的 A549 细胞和原代人肝细胞中，silvestrol 对两种分析的株均具有抑制 ZIKV 复制的潜力，尽管来自乌干达的祖先株对 silvestrol 的敏感性较低。我们的数据可能有助于确定参与控制 ZIKV 感染的宿主因素，并有助于开发抗病毒概念，这些概念可用于治疗多种病毒感染，而不会产生耐药性的风险，因为靶向宿主蛋白。
