本研究以H5N1亚型流感病毒神经氨酸酶(NA)活性位点旁的“150-空穴”为靶标,采用半柔性分子对接计算机模拟技术,设计并合成了一种绿原酸的结构类似物——4-(咖啡酰基)氨基丁酸,计算机模拟结果显示该化合物能够插入到N1“150-空穴”中并和Arg156侧链以氢键的方式结合,与N1的最佳结合自由能为-7.70 kcal.mol-1,与奥司他韦相当。同时,利用以H5N1假病毒体系为基础建立的NA抑制剂筛选模型,测定了奥司他韦、绿原酸和4-(咖啡酰基)氨基丁酸对NA的抑制作用,发现与绿原酸相比,4-(咖啡酰基)氨基丁酸显著增强了对N1型神经氨酸酶的抑制作用,但与奥司他韦仍有一定的差距。本实验初步探索了“150-空穴”作为新型神经氨酸酶抑制剂靶标的可能性,为开发新型神经氨酸酶抑制剂提供了新的思路。 In this study, targeting the “150-hole” beside the active site of the neuraminidase (NA) of influenza virus H5N1 subtype, a semi-flexible molecular docking computer simulation technique was used to design and synthesize a The structural analogue of 4- (caffeoyl) aminobutyric acid was synthesized and the results of computer simulation showed that the compound could be inserted into N1 “150-hole” and hydrogen bond with the side chain of Arg156, Good combination of free energy for -7.70 kcal.mol-1, and oseltamivir quite. At the same time, the inhibitory effect of oseltamivir, chlorogenic acid and 4- (caffeoyl) aminobutyric acid on NA was determined by using NA inhibitor screening model based on H5N1 pseudovirions. In contrast, 4- (caffeoyl) aminobutyric acid significantly enhanced the inhibitory effect on N1-neuraminidase, but there was still a gap between it and oseltamivir. This experiment tentatively explored the possibility of “150-hole ” as a target of a novel neuraminidase inhibitor and provided a new idea for developing a novel neuraminidase inhibitor.