近日,由中科院昆明植物研究所植物化学与西部植物资源持续利用国家重点实验室郝小江研究组,中科院微生物研究所植物基因组学国家重点实验室方荣祥研究组,以及中国疾病预防控制中心病毒病预防控研究所和云南省农科院生物技术研究所等四家单位联合在《美国科学院院刊》(PNAS)上发表了题为“Seco-pregnane steroids target the subgenomic RNA of alphavirus-like RNA viruses”的最新研究成果论文。
植物在漫长的进化历程中,具备了以多种机制选择性地抵御病源侵染的能力,这种能力可以通过其合成的次生代谢产物来实现。因此,从植物中直接筛选抗病毒化合物可以发现新的具有抗病毒潜力的、同时对宿主植物本身没有毒性的成分。
该项研究首次发现双裂孕烷甾体glaucogenin C及其苷类化合物选择性地抑制-正链RNA病毒如植物病毒烟草花叶病毒(TMV),动物(人)病毒辛德比斯病毒(SINV)、东方马脑炎病毒(EEEV)和盖塔病毒(GETV)等,但对其它RNA病毒或DNA病毒没有作用,且对病毒宿主没有毒性。动物体内实验证实:该类化合物能保护BALB/c小鼠不被SINV侵染致死而对小鼠没有副作用。以TMV和SINV作为模式病毒,探讨了该类化合物抗病毒的作用机制,结果表明该类化合物选择性地抑制病毒亚基因组RNA的复制,而对病毒基因组RNA的复制没有影响。该文认为:病毒亚基因组RNA可以作为发现抗病毒药物的新靶点,从两种药用植物中发现的双裂孕烷甾体glaucogenin C及其苷类化合物有可能发展成为抗-正链RNA病毒新的一类抑制剂State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, China;
State Key Laboratory of Plant Genomics, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080, China;
State Key Laboratory for Infectious Disease Prevention and Control, Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China; ¶Laboratory of Plant Virology, Yunnan Academy of Agricultural Sciences, Kunming 650223, China; and
Graduate School of the Chinese Academy of Sciences, Beijing 100049, China
Communicated by Zhu Chen, Shanghai Second Medical University, Shanghai, China, March 21, 2007 (received for review October 31, 2006)
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