中文摘要
呼吸道合胞病毒(RSV)感染严重危害人类健康,临床上尚无有效治疗RSV感染的药物。寻找高效低毒的抗病毒性炎症药物已成为当前抗病毒药物研究的一个重要方向。中药地胆草传统上一直被用来治疗呼吸道感染疾病,我们的前期研究首次发现其中的倍半萜类化合物可有效抑制RSV感染后诱发的炎症,能弥补传统抗病毒药物在病毒性炎症方面的不足,但其作用机制不明。初步的研究表明地胆草倍半萜抗RSV病毒性炎症效果显著,其作用是抗炎药吲哚美辛的数十倍;且该类成分可通过影响NLRP3的合成来抑制RSV诱发的炎症反应,与现有临床治疗RSV感染药物的作用机制明显不同;另外,该类成分有明显的构效关系,α-亚甲基-γ-丁内酯环是其关键基团。本项目拟进一步分离和鉴定地胆草属中的倍半萜类成分;评价其对RSV诱发性炎症的抑制活性,明确其构效关系;并深入研究其抑制NLRP3信号通路的作用机制,为研究和开发新型抗RSV感染药物提供科学依据。
英文摘要
Respiratory syncytial virus (RSV) seriously threatens human health, and in clinic there is no effective drug for the treatment of RSV infection. Now, searching for the high efficiency and low toxicity drugs against virus-induced inflammation has become an important direction in study of antiviral drugs. A traditional Chinese medicine Elephantopus scaber was traditionally used to treat respiratory infection diseases, our previous studies had shown that the sesquiterpenoids from this plant could effectively inhibit RSV-induced inflammation, but the mechanism was unclear. Our studies also suggested that the anti-inflammation effect of the sesquiterpenoids was significant, and it was much stronger than that of Indometacin. These compounds were found to inhibit the inflammation by regulating NLRP3 inflammsome, and the structure-activity relationship of them was obvious. This project intends to further separate and identify the sesquiterpenoids from the plants of Elephantopus genus, to evaluate their inhibitory activity on RSV-induced inflammation, to discuss the structure-activity relationship of the sesquiterpenoids, and to study the mechanism of the sesquiterpenoids against RSV-induced inflammation by regulating the NLRP3 inflammsome. This project will provide the scientific basis for developing the new antiviral drugs against RSV-induced inflammation.
