弥散性肺泡充血是流感病毒导致的病理特征之一，临床缺少有效治疗手段。随着近2年，对血小板生物功能研究的突破，发现特异性阻断血小板相关受体不仅可有效改善症状，还无出血风险，是治疗流感的新靶点。项目组前期在国家自然科学基金项目研究的基础上，从石荠苧有效部位中首次分离到6个二酮哌嗪类成分(DPKs)；部分DPKs不仅可抑制抑制病毒增殖，改善流感致小鼠肺损伤，还能抑制血小板聚集及弥散性肺泡充血，我们推测DPKs可能是石荠苧抗流感药效物质之一，其可能通过抑制血小板活化或凝聚而发挥作用，但其机制尚不清楚。本项目采用蛋白质组学和基因敲除技术，以血小板为切入点，通过构建流感感染动物和细胞模型，获取2-3个DPKs类药效物质，并从组织病理、细胞表型、信号转导和分子对接4个层次，阐明DPKs的药效强弱、构效关系及其作用机制，为中药药效物质研究及其作用机制提供一种新的视角和方法，为中药DPKs新药研发提供依据。

Pulmonary diffuse hemorrhage is one of the pathological characteristics induced by influenza virus, which is lack of effective treatment. There is a breakthrough on the biological function of platelets in the past 2 years. It is found that the specific blocking of platelet related receptors can not only improve the symptoms, but also avoid the bleeding risk, which will be the new targets for the treatment of influenza virus. In the previous projects granted by the State Natural Science Foundation, we found six diketopiperazines (DPKs) from the effective fraction of Mosla scabra. DPKs can inhibit the viral replication and improve influenza virus-induced acute lung injury, but also can inhibit platelet aggregation and improve pulmonary diffuse hemorrhage. Therefore, we hypothesized that DPKs may be one of anti-influenza virus substances in M. scabra by inhibiting platelet activation and aggregation, but the mechanism is unclear. Taking the blood platelet as the breakthrough point, this study is aimed to obtain 2 to 3 bioactivity DPKs from M. scabra on influenza virus-induced lung injury mouse model and cell model by proteomics, gene knockout and gene knockout technology. In addition, the bioactivity and structure-activity relationship of DPKs, as well as their network regulation mechanism on influenza virus-induced pulmonary diffuse hemorrhage, cell function, signal transduction and chemical structure will be investigated. The present study will reveal the antiviral effects of DPKs from herb, and provide a new perspective and method for traditional Chinese medicine, providing evidence for development of new herbal DPK drugs.