STRUCTURE-BASED DEVELOPMENT OF INHIBITORS OF VIRAL ENZYMES

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。 人类和动物的许多重要病原体属于正义单链RNA病毒。RNA聚合酶和胰凝乳蛋白酶样半胱氨酸蛋白酶等酶是病毒复制所必需的。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许多病毒酶的晶体结构，包括一些结合抑制剂的酶（例如，HCV，SARS和小核糖核酸病毒）。这一工作对于理解病毒进化、酶促机制和开发抗病毒药物具有重要意义。我们正在进行一个项目，以开发不同的和更有效的抑制剂的几种病毒酶。

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.