STRUCTURE DETERMINATION OF VIRAL NUCLEOPROTEIN COMPLEXES

病毒核蛋白复合物的结构测定

• 批准号: 8362196
• 负责人: MING LUO
• 金额: $ 0.25万
• 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/8362196
• 关键词: Avian Influenza; Bunyamwera virus; Bunyaviridae; Complex; Family; Funding; Generations; Glycoproteins; Grant; HIV; Human; Influenza; Measles virus; National Center for Research Resources; Nucleocapsid; Nucleocapsid Proteins; Nucleoproteins; Orthomyxoviridae; Paramyxoviridae; Pharmaceutical Preparations; Principal Investigator; Proteins; RNA; RNA Viruses; Rabies; Radiation; Research; Research Infrastructure; Resources; Rhabdoviridae; Source; Structure; United States National Institutes of Health; Vesicular stomatitis Indiana virus; Viral; Viral Proteins; Virus; Work; cost; design; drug candidate; influenzavirus; inhibitor/antagonist; interest; novel; 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. Our lab is focused on the study of virus nucleocapsid structure. We are interested in how structure is involved with assembly and function of negative strand RNA viruses (NSRVs). The group of NSRVs includes some of the most dangerous human pathogens, such as Ebola, rabies, avian influenza, and measles viruses. This proposal is an extension of our previous and continued work with the viral nucleocapsid (N) protein of vesicular stomatitis virus (VSV). The decameric structure of N complexed with a 90-mer of RNA has been completed. Now, complexes between the N-RNA and other VSV proteins are the focus of study. Additionally, we are continuing to expand beyond the Rhabdovirus family, to study nucleocapsid proteins of three other NSRV families, Orthomyxoviridae, Paramyxoviridae and Bunyaviridae (influenza virus, RSV and Bunyamwera virus, respectively). The structural study of the influenza nucleoprotein (NP) is complimented with the design of inhibitors against the viral glycoprotein HA. We have found a novel class of fusion inhibitors that have a potent and irreversible inhibitory effect on influenza viruses. We also continue the study of HIV CA/inhibitor complexes. These inhibitors are designed disrupt viral assembly and maturation. Here we look to transform initial hits into optimized drug leads and ultimately into second generation drug candidates.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 我们实验室致力于病毒核衣壳结构的研究。我们感兴趣的是结构如何与负链 RNA 病毒 (NSRV) 的组装和功能相关。 NSRV 包括一些最危险的人类病原体，例如埃博拉病毒、狂犬病病毒、禽流感病毒和麻疹病毒。该提案是我们之前和持续研究水泡性口炎病毒（VSV）病毒核衣壳（N）蛋白的工作的延伸。 N与90聚体RNA复合的十聚体结构已经完成。现在，N-RNA 和其他 VSV 蛋白之间的复合物是研究的焦点。此外，我们正在继续扩展到弹状病毒家族之外，研究其他三个 NSRV 家族的核衣壳蛋白，即正粘病毒科、副粘病毒科和布尼亚病毒科（分别为流感病毒、RSV 和布尼亚姆维拉病毒）。流感核蛋白 (NP) 的结构研究与病毒糖蛋白 HA 抑制剂的设计相辅相成。我们发现了一类新型融合抑制剂，对流感病毒具有有效且不可逆的抑制作用。我们还继续研究 HIV CA/抑制剂复合物。这些抑制剂旨在破坏病毒组装和成熟。在这里，我们希望将最初的命中转化为优化的先导药物，并最终转化为第二代候选药物。