Biochemical and NMR Studies of Influenza HA2

描述(由申请人提供)：病毒包膜蛋白HA1和HA2在流感进入过程中发挥关键作用。HA2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HA2的结构域可以作为体内存在的更大域的模型。这项研究的长期目标是通过核磁共振波谱进行合理的药物设计和高通量筛选，以寻找旨在破坏HA2功能从而破坏流感感染的新型抗病毒药物。具体目标是：(1)从特性良好的1968 H3毒株中产生并表征适于通过核磁共振光谱学进行生物物理特性和药物发现的HA2结构；(2)从导致迄今最致命的流感大流行的1918年HI毒株中产生并表征流感HA2结构，并且这些结构适于通过核磁共振波谱进行生物物理特性和药物发现；(3)将通过核磁共振波谱确定最有希望的HA2结构的结构和动力学性质。

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.