【摘要】 SARS冠状病毒3CL蛋白酶是SARS病毒复制过程中的主要蛋白酶,针对其开展药物设计有望得到有效的抗SARS病毒药物.本文基于SARS冠状病毒3CL蛋白酶的三维结构,对现有化学试剂及临床用药数据库进行虚拟筛选,选出可能对SARS冠状病毒3CL蛋白酶有抑制的非肽化合物进行初步活性测试,并研究了已知的人鼻病毒3C蛋白酶抑制剂对SARS冠状病毒3CL蛋白酶的活性,合成了两种母环的衍生物,得到靛红和哌嗪两类SARS冠状病毒3CL蛋白酶的抑制剂,其中一个靛红类化合物的IC50为0.76μmol·L-1;而抗组胺药哌嗪类化合物对SARS冠状病毒3CL蛋白酶及细胞培育的SARS病毒的抑制作用,提示了老药可以开发出新的用途.更多还原

【Abstract】 Severe acute respiratory syndrome(SARS)coronavirus 3C-like proteinase is the key enzyme for the maturation of the virus and has been proposed to be a key target for structure based drug design against SARS.In this paper,based on the three-dimensional structure of SARS coronavirus 3C-like proteinase,the available chemical database(ACD)and clinical drug databases were used for virtual screening,and the can-didate non-peptidic compounds were purchased or synthesized.Several human rhinovirus(HRV)3C prote-ase inhibitors were also synthesized.All the compounds were tested against SARS 3C-like proteinase bioas-say.Two types of compounds including hydroxyzine dihydrochloride,a well known antihistamine,were found to inhibit the enzyme and SARS virus in cell cultivating;one of the isatin compounds shows signifi-cant inhibition with an IC50 of(0.76±0.02)μmol·L-1.The primary result suggested that drugs in clinical usage can be developed for new purpose.更多还原