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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 我们的实验室重点是研究病毒核素结构。我们对结构如何与负链RNA病毒（NSRV）的组装和功能有关。 NSRV组包括一些最危险的人类病原体，例如埃博拉病毒，狂犬病，禽流感和麻疹病毒。该提议是我们以前和继续使用囊泡气孔病毒（VSV）的病毒核衣壳（N）蛋白的延伸。与90-MER RNA复合的N的deT型结构已经完成。现在，N-RNA和其他VSV蛋白之间的复合物是研究的重点。此外，我们正在继续扩展超越黄白菌病毒家族，研究其他三个NSRV家族的核素蛋白，分别是Orthomyxoviridae，Paramyxoviridae和Bunyaviridae（分别为流感病毒，RSV和Bunyamwera病毒）。流感核蛋白（NP）的结构研究与对病毒糖蛋白HA的抑制剂的设计相称。我们发现了一种新型的融合抑制剂，这些抑制剂对流感病毒具有有效且不可逆转的抑制作用。我们还继续研究HIV CA/抑制剂复合物。这些抑制剂设计的破坏病毒组装和成熟。在这里，我们希望将初始命中转变为优化的药物铅，并最终转变为第二代药物候选者。