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Seco-pregnane steroids target the subgenomic RNA of alphavirus-like RNA viruses

文献类型： 外文期刊

作者： Li, Yanmei 1 ; Wang, Lihua 2 ; Li, Shunlin 3 ; Chen, Xiaoying; Shen, Yuemao; Zhang, Zhongkai; He, Hongping; X 1 ;

作者机构： 1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources W China, Kunming 650204, Peoples R China

2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources W China, Kunming 650204, Peoples R China; Chinese Acad Sci, State Key Lab Plant Plant Genom, Beijing 100080, Peoples R China; Chinese Ctr Dis Control & Prevent, Inst Viral Dis Control & Prevent, State Key Lab Infect Dis Prevent & Control, Beijing 100052, Peoples R China; Yunnan Acad Agr Sci, Lab Plant Virol, Kunming 650223, Peoples R China; Chinese Acad Sci, Grad Sch, Beijing 100049, Peoples R China

3.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources W China, Kunming 650204, Peoples R China; Chinese Acad Sci, State Key Lab Plant Plant Genom, Beijing 100080, Peoples R China; Chinese Ctr Dis Control & Prevent, Inst Viral Dis Control & Prevent, State Key Lab Infect Dis Prevent & Control, Beijing 100052, Peoples R China; Yunnan Acad Agr Sci, Lab Plant Virol, Kunming 650223, Peoples R China; C

关键词： antiviral drugs;Strobilanthes cusia;Cynanchum atratum

期刊名称：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA （ 影响因子：11.205； 五年影响因子：12.291 ）

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收录情况： SCI

摘要： 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 alpha-virus-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 glyco-sides found in the two medicinal herbs have the potential for further development as antiviral agents against alphavirus-like positive-strand RNA viruses.

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