STRUCTURE-BASED DEVELOPMENT OF INHIBITORS OF VIRAL ENZYMES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 人类和动物的许多重要病原体都属于阳性单链RNA病毒。RNA聚合酶和类凝乳杆菌半胱氨酸蛋白酶是病毒复制必不可少的酶。因此，这些酶及其前体是设计抗病毒药物的理想靶点。我们和其他人已经确定了这一组中的一些病毒酶的晶体结构，包括一些带有结合抑制物的酶(例如，丙型肝炎病毒、SARS和小核糖核酸病毒)。这项工作对于了解病毒的进化、酶机制和抗病毒药物的开发具有重要意义。我们正在进行一个项目，以开发几种病毒酶的不同和更有效的抑制剂。

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. Many important pathogens of humans and animals belong to the positive-sense, single-stranded RNA viruses. Enzymes such as RNA polymerase and the chymotrypsin-like cysteine proteases are absolutely required for viral replication. Therefore, these enzymes and their precursors are ideal targets for the design of antiviral drugs. We and others have determined crystal structures of a number of viral enzymes from this group, including some with bound inhibitors (for example, HCV, SARS and picorna-viruses). This work is valuable for the understanding of viral evolution, enzymatic mechanisms and the development of anti viral drugs. We are pursuing a project to develop different and more effective inhibitors of several viral enzymes.