STRUCTURE-BASED DEVELOPMENT OF INHIBITORS OF VIRAL ENZYMES

基于结构的病毒酶抑制剂的开发

• 批准号: 8362300
• 负责人: Katherine S Bateman
• 金额: $ 0.08万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362300
• 关键词: Animals; Antiviral Agents; Binding; Cysteine Protease; DNA-Directed RNA Polymerase; Development; Enzymes; Evolution; Funding; Grant; Hepatitis C virus; Human; National Center for Research Resources; Pharmaceutical Preparations; Principal Investigator; RNA Viruses; Radiation; Research; Research Infrastructure; Resources; Severe Acute Respiratory Syndrome; Source; Structure; United States National Institutes of Health; Viral; Virus; Virus Inhibitors; Work; base; chymotrypsin; cost; design; inhibitor/antagonist; pathogen; structural biology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 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。