Biochemical and NMR Studies of Influenza HA2

流感 HA2 的生化和核磁共振研究

• 批准号: 7132489
• 负责人: Michael S. Caffrey
• 金额: $ 7.75万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7132489
• 关键词: influenza; proteins

DESCRIPTION (provided by applicant): The viral envelope proteins HA1 and HA2 play critical roles in influenza entry. HA2 mediates fusion of the viral and cellular membranes, thereby allowing entry of the influenza genetic material. The guiding hypothesis is that structural domains of HA2 can serve as models of the larger domain present in vivo. The long-term goal of this research is to perform rationale drug design and high throughput screening by NMR spectroscopy for novel antivirals that are designed to disrupt HA2 function and hence influenza infection. The specific aims are: (1) Generate and characterize influenza HA2 constructs, from the well characterized 1968 H3 strain, that are amenable for biophysical characterizations and drug discovery by NMR spectroscopy; (2) Generate and characterize influenza HA2 constructs, from the 1918 HI strain responsible for the most deadly flu pandemic to date, that are amenable for biophysical characterizations and drug discovery by NMR spectroscopy; (3) The structure and dynamic properties of the most promising HA2 constructs will be determined by NMR spectroscopy.

性状（由申请方提供）：病毒包膜蛋白HA 1和HA 2在流感病毒进入中起关键作用。HA 2介导病毒和细胞膜的融合，从而允许流感遗传物质进入。指导性假设是HA 2的结构域可以作为体内存在的较大结构域的模型。本研究的长期目标是通过NMR光谱进行合理的药物设计和高通量筛选，以获得旨在破坏HA 2功能并因此感染流感的新型抗病毒药物。具体目标是：（2）从造成迄今为止最致命的流感大流行的1918 H1毒株产生和表征流感HA 2构建体，其适合于通过NMR光谱进行生物物理表征和药物发现;（3）最有希望的HA 2构建体的结构和动力学性质将通过NMR光谱确定。