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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 find new compounds against EV71 virus. Methods: A series of oligopeptides such as dipeptide, tripeptide, tetrapeptide, pentapeptide and hexapeptide were designed by using the molecular simulation technology to target the EV71 viral pocket of 3C protease. Oligopeptide compounds with high docking score Anti-EV71 virus activity screening. Results: The docking score of pentapeptide was higher than that of other series of oligopeptides, which showed that pentapeptide compounds had stronger bonding force with EV71 virus 3C protease. Two pentapeptide compounds 25 and 16 with higher scores were synthesized in this study. The anti-EV71 activity in vitro showed that the activity of compound 25 was stronger (EC50 = 1.36μmol·L-1, CC50 = 211.94μmol·L-1, SI = 155.84), while compound 16 showed no significant activity. Conclusion: Pentapeptide compound 25 can be used as a new framework against EV71 virus for further study.