新型抗EV71病毒3C蛋白酶抑制药的设计、合成及其活性

Design,Synthesis and Antiviral Activity of Novel EV71 3C Protease Inhibitors

目的:寻找抗EV71病毒新化合物。方法:采用分子模拟技术,以EV71病毒3C蛋白酶活性口袋为靶,设计二肽、三肽,四肽,五肽和六肽等多个系列寡肽化合物,合成对接评分较高的寡肽化合物并进行抗EV71病毒活性筛选。结果:五肽对接评分高于其他系列寡肽,显示五肽化合物与EV71病毒3C蛋白酶有更强的键合力。研究中合成了两个评分较高的五肽化合物25和化合物16,体外抗EV71病毒活性实验显示化合物25活性较强(EC50=1.36μmol·L-1,CC50=211.94μmol·L-1,SI=155.84),而化合物16则无明显活性。结论:五肽化合物25可作为抗EV71病毒新骨架开展进一步研究。

Objective：To explore novel compounds with anti-EV71 activity. Methods： A series of oligopeptides were designed based on the active groove of the EV71 3C protease using molecular simulation technology. Furthermore, some oligopeptides were syn-thesized and tested for the inhibition ability against EV71 in vitro. Results：Pentapeptides had higher binding affinity to the EV71 3C protease than the other oligopeptides, such as compounds 25 and 16. Therefore, compounds 25 and 16 were synthesized and tested in vitro for the anti-EV71 activity, and compound 25 exhibited potent anti-EV71 activity（EC50 =1. 36 μmol·L-1, CC50 =211. 94 μmol ·L-1, SI=155. 84）, while compound 16 had no evident effect on EV71. Conclusion： It is worthy of further investigation on com-pound 25 as a novel scaffold of anti-EV71inhibitor.