TARGETTING CYSTEINE PROTEINASES OF THE SARS-ASSOCIATED CORONAVIRUS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。SARS冠状病毒是一种高传染性的新出现的致病病毒，我们建立了一种基于荧光的高通量半胱氨酸蛋白酶3clPro的检测方法。利用该方法，我们筛选了半胱氨酸蛋白酶抑制剂文库，并鉴定了两个在低微摩尔浓度下对该酶有抑制作用的化合物。合作者还在病毒复制测试中测试了这些化合物，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化合物与蛋白酶的复合体的共晶结构。

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.