MOUSE HEPATITIS CORONAVIRUS RECEPTOR-BINDING DOMAIN

小鼠肝炎冠状病毒受体结合域

• 批准号: 8361713
• 负责人: Fang Li
• 金额: $ 1.1万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361713
• 关键词: Affinity; Animals; Antiviral Agents; Binding; Biological Assay; CEACAM1a; Cell Adhesion Molecules; Cell fusion; Cells; Complex; Coronavirus; Coronavirus spike protein; Evolution; Funding; Grant; Health; Hepatitis; Human; Infection; Medical; Murine hepatitis virus; Mus; N-terminal; National Center for Research Resources; Pattern recognition receptor; Peptidyl-Dipeptidase A; Principal Investigator; Proteins; Research; Research Infrastructure; Resources; SARS coronavirus; Source; Structure; Surface Plasmon Resonance; United States National Institutes of Health; Viral; Virus Diseases; Virus Receptors; alanine aminopeptidase; coronavirus receptor; cost; novel; receptor; receptor binding; respiratory; structural biology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Coronaviruses, a significant health threat to humans and other animals, have perplexing receptor recognition patterns. Human NL63 respiratory coronavirus (NL63-CoV) is the only group-I coronavirus known to use angiotensin-converting enzyme 2 (ACE2) as its receptor. The other group-I coronaviruses use aminopeptidase-N (APN) from their respective hosts. Curiously, ACE2 is also used by group-II human SARS coronavirus (SARS-CoV). Another group-II coronavirus, mouse hepatitis virus (MHV), uses a cell adhesion molecule CEACAM1a as its receptor. Defined receptor-binding domains (RBDs) on the spike proteins of coronaviruses are responsible for high-affinity binding to their receptors. MHV is the only coronavirus that uses the N-terminal domain of its spike protein as its RBD, whereas all other coronaviruses with known receptors use other domains of their spike proteins as their RBDs. This research investigates how coronaviruses recognize their receptors and how they interact with receptors from multiple hosts. Specifically, we will determine crystal structures of viral RBDs complexed with their receptor, use surface plasmon resonance to examine interactions between viral RBDs and their receptors, and use pseudotyped viral infection and cell-cell fusion assays to examine interactions between viral spike proteins and their receptors. This research has significant scientific and medical implications. It will not only explore novel principles governing viral evolution, virus-receptor interactions, viral host ranges and cross-species infections, but also guide antiviral efforts.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 冠状病毒对人类和其他动物的健康构成重大威胁，其受体识别模式令人困惑。人类NL63呼吸道冠状病毒（NL63-CoV）是已知唯一使用血管紧张素转换酶2（ACE2）作为受体的I类冠状病毒。其他 I 组冠状病毒使用来自各自宿主的氨肽酶-N (APN)。奇怪的是，II 类人类 SARS 冠状病毒 (SARS-CoV) 也使用 ACE2。另一种II类冠状病毒，小鼠肝炎病毒（MHV），使用细胞粘附分子CEACAM1a作为其受体。冠状病毒刺突蛋白上确定的受体结合域（RBD）负责与其受体的高亲和力结合。 MHV 是唯一使用其刺突蛋白的 N 端结构域作为其 RBD 的冠状病毒，而所有其他具有已知受体的冠状病毒均使用其刺突蛋白的其他结构域作为其 RBD。这项研究调查了冠状病毒如何识别其受体以及它们如何与多个宿主的受体相互作用。具体来说，我们将确定病毒 RBD 与其受体复合的晶体结构，使用表面等离子共振来检查病毒 RBD 与其受体之间的相互作用，并使用假型病毒感染和细胞-细胞融合测定来检查病毒刺突蛋白与其受体之间的相互作用。这项研究具有重大的科学和医学意义。它不仅将探索控制病毒进化、病毒-受体相互作用、病毒宿主范围和跨物种感染的新原理，还将指导抗病毒工作。