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

2019年新型冠状病毒迅速传播，成为全球大流行。像SARS-CoV-2这样的包膜病毒的感染需要将病毒膜与宿主细胞膜融合。这项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。对这一过程的理解将为疫苗和抗体的积极发展提供信息。科学活动将为PI和他的实验室成员提供一个特殊的机会，向当地高中生展示基础研究如何帮助技术开发，以保障公众健康和安全。核磁共振(核磁共振)引导的SARS-CoV-2对接到人体细胞的研究将提供第一个与病毒融合肽结合的脂类双层坐标的结构模型，从而提供融合肽操纵脂类的细节。这一结果将促使免疫开发人员考虑将融合肽的存在和形式作为抗原。融合肽的非结合状态的动态结构应代表其作为暴露在溶剂中的抗原的行为，其双层相关状态的结构将告知双分子层外的抗体可访问的位置。这一快速奖项是由分子和细胞生物科学部门的分子生物物理学计划利用冠状病毒援助、救济和经济安全(CARE)法案的资金颁发的。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.