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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Seco-pregnane steroids target the subgenomic RNA of alphavirus-like RNA viruses
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Seco-pregnane steroids target the subgenomic RNA of alphavirus-like RNA viruses

机译：山茱pre类固醇靶向α病毒样RNA病毒的亚基因组RNA

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Plants have evolved multiple mechanisms to selectively suppress pathogens by production of secondary metabolites with antimicrobial activities. Therefore, direct selections for antiviral compounds from plants can be used to identify new agents with potent antiviral activity but not toxic to hosts. Here, we provide evidence that a class of compounds, seco-pregnane steroid glaucogenin C and its monosugar-glycoside cynatratoside A of Strobilanthes cusia and three new pantasugar-glycosides of glaucogenin C of Cynanchum paniculatum, are effective and selective inhibitors to alphavirus-like positive-strand RNA viruses including plant-infecting tobacco mosaic virus (TMV) and animal-infecting Sindbis virus (SINV), eastern equine encephalitis virus, and Getah virus, but not to other RNA or DNA viruses, yet they were not toxic to host cells. In vivo administration of the compounds protected BALB/c mice from lethal SINV infection without adverse effects on the mice. Using TMV and SINV as models, studies on the action mechanism revealed that the compounds predominantly suppress the expression of viral subgenomic RNA(s) without affecting the accumulation of viral genomic RNA. Our work suggested that the viral subgenomic RNA could be a new target for the discovery of antiviral drugs, and that seco-pregnane steroid and its four glycosides found in the two medicinal herbs have the potential for further development as antiviral agents against alphavirus-like positive-strand RNA viruses.
机译：植物已经进化出多种机制来通过产生具有抗菌活性的次级代谢产物来选择性抑制病原体。因此，从植物中直接选择抗病毒化合物可用于鉴定具有有效抗病毒活性但对宿主无毒的新药剂。在这里，我们提供证据表明，一类化合物，山核桃脂甾体类青素生成素C及其Strobilanthes cusia的单糖-糖苷cynatratoside A和三叶草的青素生成素C的三种新的Pantasugar-糖苷是有效的和选择性的α-病毒样阳性抑制剂链RNA病毒，包括植物感染的烟草花叶病毒（TMV）和动物感染的信德比斯病毒（SINV），东部马脑炎病毒和格塔病毒，但对其他RNA或DNA病毒无毒，但对宿主细胞无毒。化合物的体内施用保护了BALB / c小鼠免于致命的SINV感染，而对小鼠没有不利影响。使用TMV和SINV作为模型，对作用机理的研究表明，这些化合物主要抑制病毒亚基因组RNA的表达，而不会影响病毒基因组RNA的积累。我们的工作表明，病毒亚基因组RNA可能成为发现抗病毒药物的新靶标，并且在两种草药中发现的山核桃-孕烯类固醇及其四种糖苷有可能进一步发展为抗甲病毒样阳性抗体的抗病毒剂。链RNA病毒。

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