EAGER: Structure and Assembly of SARS-CoV2 nucleocapsid phosphoprotein N

该研究项目旨在了解SARS-CoV-2的N蛋白如何在病毒感染和传播中发挥其基本功能。阐明N蛋白的结构和性质可以为对抗COVID-19大流行的药物设计开辟新途径，并为抗病毒治疗策略增添新工具。更广泛的影响计划是通过Skype a Scientist和TikTok视频等社交媒体活动向年轻一代宣传和教育病毒传播和预防科学。病毒基因组核衣壳磷蛋白N在感染周期的多个过程中发挥着关键作用：N蛋白在核衣壳组装中保护和包装病毒RNA，在病毒粒子组装中与刺突蛋白的内域相互作用，在病毒体包装和成熟过程中与结构膜蛋白M结合，并与引起感染性病毒颗粒复制的蛋白酶结合。该项目的目标是利用核磁共振等高分辨率技术确定SARS-CoV-2 N蛋白的结构和动力学，利用蛋白质：RNA交联和生物信息学分析确定病毒包装的结构特征，并确定N的磷酸化对其结构的影响，其与其他蛋白质的相互作用及其作为RNA伴侣的作用。这种对N-蛋白结构-功能的全面研究将有助于开发在SARS-CoV-2生命周期的不同阶段阻断其的创新方法。EAGER奖由分子和细胞生物科学部的遗传机制计划颁发，使用冠状病毒援助，救济，经济安全（CARES）该奖项反映了NSF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进行评估，被认为值得支持的搜索.

The research project is aimed at understanding how the N-protein of the SARS-CoV-2 performs its essential functions in viral infection and transmission. Elucidating the structure and properties of N-protein can open novel avenues of drug design to combat the COVID-19 pandemic, and add new tools to the repertoire of anti-viral therapeutic strategies. The broader impact plan is to inform and educate the younger generation about the science of virus transmission and prevention using social media activities such as Skype a Scientist and TikTok videos.The viral genome nucleocapsid phosphoprotein N plays critical roles in multiple processes of the infection cycle: N-protein protects and packages viral RNA in nucleocapsid assembly, interacts with the inner domain of spike protein in virion assembly, binds to structural membrane protein M during virion packaging and maturation, and binds to proteases causing replication of infective virus particles. The goals of the project are to determine the structure and dynamics of SARS-CoV-2 N protein using high resolution techniques such as NMR, identify structural features of viral packaging using protein:RNA cross linking and bioinformatic analyses, and determine the effect of phosphorylation of N on its structure, its interactions with other proteins and its role as an RNA chaperone. This comprehensive approach to N-protein structure-function will enable development of innovative methods to block SARS-CoV-2 at different stages of its life cycle.This EAGER award is made by the Genetic Mechanisms 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.