新型传染性胃肠炎病毒小分子抑制剂
Novel small-molecule inhibitors of transmissible gastroenteritis virus.
作者信息
Yang Cheng-Wei, Yang Yung-Ning, Liang Po-Huang, Chen Chi-Min, Chen Wei-Liang, Chang Hwan-You, Chao Yu-Sheng, Lee Shiow-Ju
机构信息
Division of Biotechnology and Pharmaceutical Research, National Health Research Institute, 35, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, Republic of China.
出版信息
Antimicrob Agents Chemother. 2007 Nov;51(11):3924-31. doi: 10.1128/AAC.00408-07. Epub 2007 Aug 20.
Abstract
We used swine testicle (ST) cells infected with transmissible gastroenteritis virus (TGEV) and an indirect immunofluorescent assay with antibodies against TGEV spike and nucleocapsid proteins to screen small-molecule compounds that inhibit TGEV replication. Analogues of initial hits were collected and subjected to a 3CL protease (3CL(pro)) inhibition assay with recombinant 3CL(pro) and a fluorogenic peptide substrate. A series of benzothiazolium compounds were found to have inhibitory activity against TGEV 3CL(pro) and to exert anti-TGEV activities in terms of viral protein and RNA replication in TGEV-infected ST cells, with consequent protection of TGEV-infected ST cells from cytopathic effect by blocking the activation of caspase-3.
摘要
我们使用感染了传染性胃肠炎病毒（TGEV）的猪睾丸（ST）细胞，并采用针对TGEV刺突蛋白和核衣壳蛋白的抗体进行间接免疫荧光测定，以筛选抑制TGEV复制的小分子化合物。收集初始命中化合物的类似物，并使用重组3CL蛋白酶（3CL(pro)）和荧光肽底物进行3CL蛋白酶抑制测定。发现一系列苯并噻唑鎓化合物对TGEV 3CL(pro)具有抑制活性，并在TGEV感染的ST细胞中对病毒蛋白和RNA复制发挥抗TGEV活性，从而通过阻断caspase-3的激活保护TGEV感染的ST细胞免受细胞病变效应的影响。
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