RAPID: Determination of SARS-CoV-2 Spike Glycoprotein Palmitoylation and its Contribution to Virus-Cell Fusion and Surface Protein-Protein Interactions

RAPID：测定 SARS-CoV-2 刺突糖蛋白棕榈酰化及其对病毒-细胞融合和表面蛋白-蛋白质相互作用的贡献

• 批准号: 2031068
• 负责人: Neal Devaraj
• 金额: $ 20万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-15 至 2022-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2031068&HistoricalAwards=false
• 关键词: RAPID; Determination; SARS; CoV; Spike

Coronaviruses, such as SARS-CoV-2, the causative agent of COVID-19, are enveloped RNA viruses that encode three envelope proteins – spike glycoprotein (S), envelope protein (E), and membrane protein (M). Of special interest are the coronavirus S proteins, which coat the surface of the virus and form the distinctive “corona” structure. S proteins are responsible for interacting with specific receptors on the surface of host cells, thus initiating virus entry and infection. This project examines the role of S protein palmitoylation, a chemical modification of the S protein with the addition of a fatty acid, in the fusion of the virus to the host cell, and virus infectivity. Understanding the role of S protein palmitoylation in virus infectivity can lead to the development of new therapeutic targets that block the infectivity of COVID-19. This project will also contribute to the interdisciplinary training of two graduate students. In addition, PI will engage in outreach activities with the San Diego educational community and the public, in part through a collaboration with the San Diego Science project, a K-12 professional development and teacher support organization.The goal of this RAPID proposal is to explore how palmitoylation mediates viral entry and infection of SARS-CoV-2, through S-mediated membrane fusion and host cell receptor interactions. The PIs propose that palmitoylation of the SARS-CoV-2 spike glycoprotein is necessary for these important viral processes that lead to host infection. The specific aims of this project are: (1) Determining the cysteine residues that are palmitoylated in the SARS-CoV-2 spike glycoprotein. (2) Characterizing the palmitoylation-dependence of S protein localization as well as S-mediated virus-cell fusion. (3) Evaluating the palmitoylation-dependent change in protein-protein interactions between host cell surface receptors and the novel coronavirus S protein. Understanding the functional outcomes of S protein palmitoylation can help better understand the role of palmitoylation in cellular dynamics and function and possibly spur development of novel therapeutics for the treatment of COVID-19.This RAPID award is made by the Cellular Dynamics and Function 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.

冠状病毒，例如SARS-COV-2，COVID-19的病因，是包膜的RNA病毒，它们编码三种包膜蛋白 - Spike糖蛋白（S），包膜蛋白（E）和膜蛋白（M）。特别感兴趣的是冠状病毒蛋白，它们覆盖病毒的表面并形成独特的“电晕”结构。 S蛋白负责与宿主细胞表面上的特定受体相互作用，从而引发病毒的进入和感染。该项目研究了S蛋白棕榈酰化的作用，S蛋白质棕榈酰化是S蛋白质的化学修饰，并添加脂肪酸，在病毒与宿主细胞融合和病毒感染中的作用。了解S蛋白棕榈酰化在病毒感染中的作用会导致开发阻断COVID-19感染的新治疗靶标。该项目还将为两名研究生的跨学科培训做出贡献。此外，PI将通过与San Diego Science Project（K-12专业发展和教师支持组织的合作）与圣地亚哥教育社区和公众进行外展活动。这项快速提案的目的是通过S介导的SARS-COV-2探索SARS-COV-2的病毒式进入和通过S介导的膜膜融合式蜂窝融合器互动。 SARS-COV-2尖峰糖蛋白的PIS提案对于这些导致宿主感染的重要病毒过程是必需的。该项目的具体目的是：（1）确定在SARS-COV-2尖峰糖蛋白中被棕榈酰化的半胱氨酸保留。 （2）表征S蛋白定位以及S介导的病毒细胞融合的棕榈酰化依赖性。 （3）评估宿主细胞表面受体与新型冠状病毒蛋白之间蛋白质 - 蛋白质相互作用的棕榈酰化依赖性变化。了解S蛋白棕榈酰化的功能结果可以帮助更好地理解棕榈酰化在细胞动态和功能中的作用，并可能刺激新疗法的治疗方法，用于治疗covid-covid-59。该快速奖励是通过使用分子和细胞生物科学的划分在Coronavirus Aids and Security and Coref的资金的基金和经济性的基金中获得的细胞动力学和功能计划，并进行了经济，并允许。法定使命，并通过评估诚实地认为，使用基金会的智力优点和更广泛的影响审查标准。