RAPID: Structure of Membrane-Bound Fusion Peptide of SARS-CoV-2 Required for Infection

2019年新型冠状病毒传播迅速，成为全球大流行。被包膜病毒感染，如SARS-CoV-2，需要病毒膜与宿主细胞膜融合。NSF快速反应研究（Rapid）项目将支持研究冠状病毒融合肽与细胞膜结合前后的特征。对这一过程的了解将为疫苗和抗体的积极开发提供信息。科学活动将为私家侦探和他的实验室成员提供一个特别的机会，向本地高中学生展示基础研究如何协助科技发展，以保障公众健康和安全。核磁共振（NMR）引导的SARS-CoV-2对接人类细胞的研究将提供与病毒融合肽结合的脂质双层坐标的第一个结构模型，从而提供融合肽对脂质操纵的细节。该结果将促使免疫开发者考虑融合肽作为抗原的存在和形式。融合肽的非结合状态的动态结构应该代表其作为溶剂暴露抗原的行为，而其双分子层相关状态的结构将告知双分子层外抗体可接近的位点。该RAPID奖由分子和细胞生物科学部分子生物物理学项目利用《冠状病毒援助、救济和经济安全（CARES）法案》的资金设立。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The 2019 novel coronavirus spread quickly and became a global pandemic. Infection by an enveloped virus, like SARS-CoV-2, requires fusion of the viral membrane with a host cell membrane. This NSF Rapid Response Research (RAPID) project will support studies to characterize a coronavirus fusion peptide before and after it binds to the cell membrane. The understanding of this process will inform the active development of vaccines and antibodies. The scientific activities will provide a special opportunity for the PI and his lab members to show local high school students how basic research can assist technology development to safeguard public health and safety.The nuclear magnetic resonance (NMR)-guided studies of SARS-CoV-2 docking into the human cells will provide the first structural models of lipid bilayer coordinates bound to a viral fusion peptide, thereby providing details of fusion peptide manipulation of the lipids. The results will prompt immune developers to consider the presence and format of the fusion peptide as antigen. The dynamic structure of the unbound state of the fusion peptide should represent its behavior as a solvent-exposed antigen and the structure of its bilayer-associated state will inform about sites accessible to antibodies outside the bilayer. This RAPID award is made by the Molecular Biophysics Program in the Division of Molecular and Cellular Biosciences, using funds from the Coronavirus Aid, Relief, and Economic Security (CARES) Act.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.