小瓜虫病是危害最大的鱼类寄生虫病之一，自孔雀石绿和汞盐被禁用以来尚无有效的药物，因此，该病的药物防治研究一直是水产领域的研究热点。我们前期发现天然活性分子-厚朴酚，不仅具有优良抗虫活性，而且结构简单易于合成，是目前最理想的先导物。然而缺乏对药理活性特征元素及其作用机制的表征和理解极大地限制药物研发的最关键环节-先导物的优化。本项目以此为出发点，基于前期鉴定的抗小瓜虫药物靶点-精氨酸酶，通过构建抑酶活性构效关系和药效团模型确证药效团特征元素及空间分布，并运用等温滴定量热分析等方法确定药效团与精氨酸酶互作及结合模式，揭示抑制机理；此外，运用代谢组学等技术评价药效团与精氨酸酶互作对小瓜虫多胺代谢通路的影响，以阐述其抗虫分子机制。本项目的研究可以为抗小瓜虫先导物的优化提供指导，缩短药物开发周期，降低开发成本，而且还可以为其他水产药物的研发提供新思路、新策略，具有重要的科学意义和应用价值。

Ichthyophthiriasis is one of the most serious fish parasitic diseases. The effective drugs are unavailable since malachite and mercurate are banned, therefore, studies on drugs for prevent and treatment of this disease are always research focuses in aquaculture. Recently, we found a natural active molecule – magnolol, with high anti-parasitic activity, simple chemical structure and easy artificial synthesis. It is considered as an ideal lead compound. However, lack of understanding of action mechanism of this lead compound limits its chemical structure optimization, the most key link for new drug discovery. This study, based on the identification of anti-parasitic target – arginase, is to determine pharmacophore characteristics and its spatial distribution using QSAR and pharmacophore model, and also evaluate the interaction between pharmacophore and arginase through isothermal titration thermal analysis and other methods, suggesting the precise inhibition mechanism of arginase. Finally, this study is to demonstrate the effect of this interaction on polyamine pathway of Ichthyophthirius multifiliis, illustrating the anti-parasitic mechanism of this pharmacophore. The study can not only provide guidance for optimization of lead compound, shorten development cycle for anti-parasitic drug, and reduce the cost, but also provide the new thinking and strategy for the development of other fishery drugs, showing important scientific significance and application value.