STRUCTURE-BASED DEVELOPMENT OF INHIBITORS OF VIRAL CHYMOTRYPSIN-LIKE PROTEASES

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。单链正链RNA病毒的病毒类糜蛋白酶是抗病毒药物设计的理想靶点。这些酶有一个独特的机制，大多数具有不同于所有已知的哺乳动物蛋白水解酶的切割专一性。病毒的蛋白水解酶也是病毒复制必不可少的。人类和动物的许多重要病原体都属于这类病毒。我们和其他人已经确定了一些病毒类糜蛋白酶的晶体结构，包括一些带有结合抑制剂的酶。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，以开发几种不同的病毒蛋白水解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. The viral chymotrypsin-like proteases of positive-sense, single-stranded RNA viruses are an ideal target for the design of antiviral drugs. The enzymes have a unique mechanism and most have a cleavage specificity that is different from that of all known mammalian proteases. The viral proteases are also absolutely required for viral replication. Many important pathogens of humans and animals belong to this group of viruses. We and others have determined crystal structures of a number of viral chymotrypsin-like proteases, including some with bound inhibitors. 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 different viral proteases.