TARGETTING CYSTEINE PROTEINASES OF THE SARS-ASSOCIATED CORONAVIRUS

针对 SARS 相关冠状病毒的半胱氨酸蛋白酶

• 批准号: 7955484
• 负责人: Charles Scott Craik
• 金额: $ 0.89万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7955484
• 关键词: Biological Assay; Complex; Computer Retrieval of Information on Scientific Projects Database; Cysteine Protease; Enzymes; Fluorescence; Funding; Grant; Imagery; Informatics; Institution; Libraries; Peptide Hydrolases; Process; Research; Research Personnel; Resources; SARS coronavirus; Source; Structure; Testing; United States National Institutes of Health; Viral; base; biocomputing; inhibitor/antagonist

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 SARS冠状病毒是一种高度传染性的新型致病性病毒，我们建立了一种高通量的半胱氨酸蛋白酶3clpro的荧光酶法。使用该测定，我们筛选了半胱氨酸蛋白酶聚焦抑制剂文库，并鉴定了两种在低微摩尔浓度下抑制酶的化合物。这些化合物也由合作者在病毒复制试验中进行了测试，发现它们也能抑制病毒复制。最后，我们正在解决我们最有前途的化合物与蛋白酶复合的共晶结构。