TARGETTING CYSTEINE PROTEINASES OF THE SARS-ASSOCIATED CORONAVIRUS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。sars相关冠状病毒是一种传染性很强的新发致病性病毒。我们已经开发了一种高通量荧光酶法检测必需半胱氨酸蛋白酶3clpro。利用这种方法，我们筛选了半胱氨酸蛋白酶集中抑制剂文库，并鉴定了两种在低微摩尔浓度下抑制该酶的化合物。合作者还在病毒复制试验中对这些化合物进行了测试，发现它们也能抑制病毒复制。最后，我们正在解决我们最有希望的复合物与蛋白酶的共晶结构。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The SARS-associated Coronavirus is a highly infectious emerging pathogenic virus.We have developed a high-thoughput fluorescence-based enzymatic assay for the essential cysteine proteinase 3clpro. Using this assay we screened a cysteine proteinase focused inhibitor library and identified two compounds which inhibit the enzyme at low micromolar concentrations. These compounds were also tested in a viral replication assay by collaborators and found to inhibit viral replication as well. Finally we are in the process of solving a co-crystal structure of our most promising compound in complex with the proteinase.