云南产豪猪刺靶向性抗植物病毒活性成分研究

Plant virus disease seriously threaten agricultural production.Researching and producing plant virus inhibitor is one of the important undertakings in the field of plant virus disease prevention.The Mountains area of south-west china is rich in wild plants of Berberis Julianae Schneid which was previously screened and founded to be good antiphytoviral activity. Starting from the interaction between virus and host in infection and based on the mechanism of pharmacology, new screening approaches (model) targeting at the key step of combination between virus-RNA and ribosome has been developed to study the mechanism of antiphytoviral actions,active components and structure-activity relationship of Berberis Julianae Schneid in the previous research. Studies on mechanism of antiphytoviral actions will be carried out by target activity testing after construction of molecular system targeting at the key step of combination between virus-RNA and ribosome , which action to target also will be verified at cellular, tissue, and whole plants level. Based on bioassay of activity screening,studies on active components with antiphytoviral activity in Berberis Julianae Schneid will be performed using the methods of tracing, isolation, purification and identification of compound. At the same time, the structure of active components also will be determined by using modern separation technology and modern chemical analysis method such as MS, NMR, and so on. Lastly, the structure-activity relationship of targeted-active compound will be analyzed. Scientific basis for the comprehensive utilization of Berberis Julianae Schneid will be provided and the groundwork for the exploitation of antiviral lead compound with high-effective, low-adverse , strong specificity and self-owned intellectual property rights will be laid in this research project.

病毒病严重威胁农业生产，开发有效的病毒抑制剂是农业病害防治领域的重要工作。豪猪刺为小檗属药用植物，在西南山区资源丰富,前期研究发现云南产豪猪刺具有良好的抗植物病毒活性。本研究从病毒与寄主互作关系出发，以病毒核酸与核糖体识别结合这个关键步骤作为抗病毒活性作用靶点，进行抗病毒活性物研究，揭示豪猪刺抗病毒活性机制及其靶向性有效成分，为其综合利用以及为高效、低毒、特异性强并具有自主知识产权的抗病毒活性先导物的研发提供科学依据。项目研究以分子靶点及药理学基础构建体系，并针对靶点水平进行抑制活性检测，再结合细胞、组织和整株水平进行抗病毒活性验证，揭示抗病毒活性物的靶向性作用机制；组分研究以活性筛选为基础结合抗病毒活性物分离纯化，对其进行活性追踪，并采用质谱、核磁共振等波谱技术结合理化性质进行结构鉴定，弄清对靶标具有抑制活性的成分，并对活性成分进行初步构效分析，探索对靶点具有抑制活性组分的结构特点。

病毒病严重威胁农业生产，开发有效的病毒抑制剂是农业病害防治领域的重要工作。豪猪刺为小檗属药用植物，具有良好的抗植物病毒活性。在西南山区资源丰富。本研究从病毒与寄主互作关系出发，以病毒核酸与核糖体识别结合这个关键步骤作为抗病毒活性作用靶点，进行抗病毒活性物研究，揭示豪猪刺抗病毒活性机制及其靶向性有效成分，为其综合利用以及为高效、低毒、特异性强并具有自主知识产权的抗病毒活性先导物的研发提供科学依据。本项目以病毒核酸和核糖体结合为药物抑制调控靶标，利用离体麦胚蛋白翻译系统构建病毒核酸和核糖体微量结合反应研究体系，采用实时荧光定量PCR（real time quantitative PCR）和微量体系短距离高速离心分离技术，以烟草花叶病毒（TMV）作为药剂筛选的供试病毒，对RNA 上相对保守的病毒外壳蛋白基因作为检测对象，成功建立起了可用于进行病毒核酸和核糖体结合为靶标的新颖药物筛选研究方法。利用靶向性研究体系并通过组织和整体抗病毒活性进行验证，对云南多样性中草药抗病毒活性研究显示：豪猪刺具有良好的靶向性抗病毒活性，在宏观组织层面也表现相应的抗病毒活性，对病毒核酸和核糖体结合过程为靶标，抑制病毒侵染复制蛋白合成，有效阻断病毒侵染复制是其抗病毒活性的主要作用机制。除豪猪刺外，项目在云南多样性中草药抗病毒研究中还还显示大黄、菘蓝、蔓荆子、接骨木、独活、金银花、滇黄精也具有一定的靶向性抗病毒活性。豪猪刺靶向性抗病毒活性成分追踪和结构鉴定显示，主要的活性成分是小檗碱和药根碱，初步构效分析显示，小檗碱和药根碱共同的生物碱结构是抑制病毒核酸与核糖体的结合靶向活性的药理基础，是靶向性抗植物病毒药剂开发中值得关注的先导，小檗碱靶点抑制活性为药根碱的近7倍,基团结构差异可为先导结构优化提供思路指导。

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