SARS Coronavirus: Inhibition of Entry

SARS 冠状病毒：禁止进入

• 批准号: 6904478
• 负责人: Kathryn V Holmes
• 金额: $ 171.57万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-15 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6904478
• 关键词: SARS virus; antiviral agents; communicable disease control; host organism interaction; protein protein interaction; severe acute respiratory syndrome; virus infection mechanism; virus protein; virus receptors

DESCRIPTION (provided by applicant): The Sudden Acute Respiratory Syndrome (SARS) epidemic has spread to 30 countries and killed more than 800 people in the 7-month period from November 2002, to June 2003. The epidemic is a major public health emergency that has closed hospitals and schools and caused quarantines, travel advisories, and severe economic losses. No drugs or vaccines with proven efficacy are available to treat or prevent SARS. Little is known about the new, emerging coronavirus (SARS-CoV) that apparently jumped from wild animals into humans, and is now transmitted from person to person. The 6 principal investigators on this Program Project Grant have planned a coordinated analysis of the spike (S) glycoprotein on the envelope of the SARS-coronavirus to learn what species the virus can potentially infect, study how the S protein works as a molecular key to allow the virus to enter host cells, and develop new anti-viral drugs and vaccines to combat SARS-CoV. The first goals are to identify the cellular receptor for the virus, learn how it initiates virus infection, and develop antibodies and candidate anti-viral drugs that block virus infection of human cells. Dr. Holmes, who has studied receptors for other human and animal coronaviruses intensively, is the principal investigator of this Program Project Grant and Project 1. Dr. DeMartini (Project 2) has studied how viruses cause diseases of the lung in animals. He will identify animals susceptible to SARS-CoV infection, and study SARS lung pathology. Dr. Hodges (Project 3) and Dr. Wang (Project 4) will study the viral spike protein using biophysical, biochemical and functional assays with Dr. Holmes (Project 1), and by X-ray crystallography to learn what parts of the protein bind to the receptor, where antibodies target the spike, and how the spike causes membrane fusion. Dr. Wentworth (Project 5) and Dr. Mason (Project 6) will develop transgenic mice that express the human receptor for SARS-CoV and use them to learn how SARS-CoV causes disease. Mr. Shallow, (Administrative Core A) will coordinate the administration of the Projects that will be done in 5 institutions, and Dr. Holmes will coordinate the scientific interactions between the Projects. Dr. Pearson (Virus Core B) will work with the infectious SARS-CoV in the Biosafety Level 3 lab in collaboration with investigators from all of the other projects. Dr Gill (Protein Core C) will direct the synthesis and purification of viral spike proteins, receptor proteins and antibodies that are essential for each of these projects. This research will help to explain the origin of SARS-CoV, explain the pathology of SARS, develop candidate vaccines and drugs against SARS, and test them in new animal models for SARS.

描述（由申请人提供）：突然的急性呼吸综合症（SARS）流行病已经传播到30个国家，并在2002年11月至2003年6月的7个月中丧生，炸死了800多人。流行病是一种主要的公共卫生紧急情况，已关闭医院和学校，并造成了隔离，旅行咨询和严重的经济损失。没有可用于治疗或预防SARS的药物或疫苗。对新兴的冠状病毒（SARS-COV）显然从野生动物跳入人类，现在已经从一个人传播到人，知之甚少。 The 6 principal investigators on this Program Project Grant have planned a coordinated analysis of the spike (S) glycoprotein on the envelope of the SARS-coronavirus to learn what species the virus can potentially infect, study how the S protein works as a molecular key to allow the virus to enter host cells, and develop new anti-viral drugs and vaccines to combat SARS-CoV.第一个目标是鉴定病毒的细胞受体，了解其启动病毒感染的方式，并开发抗体和候选抗病毒药物，以阻止人类细胞病毒感染。霍姆斯博士强烈研究了其他人类和动物冠状病毒的受体，他是该计划项目赠款和项目1的主要研究人员。Demartini博士（项目2）研究了病毒如何引起动物肺部疾病。他将识别容易患SARS-COV感染的动物，并研究SARS肺病理学。 Hodges博士（项目3）和Wang博士（项目4）将使用Holmes博士（项目1）以及X射线晶体学研究生物物理，生化和功能分析，研究病毒尖峰蛋白，以了解蛋白质的各个部分与受体结合，抗体靶向尖峰以及尖峰的含量以及如何引起膜膜构成膜的膜。 Wentworth博士（项目5）和Mason博士（项目6）将开发向SARS-COV表达人体受体的转基因小鼠，并使用它们来了解SARS-COV如何引起疾病。浅水先生（行政核心A）将协调将在5个机构中进行的项目的管理，福尔摩斯博士将协调项目之间的科学互动。 Pearson博士（病毒核心B）将与其他所有项目的调查人员合作，在Biosafety 3级实验室中与感染性SARS-COV合作。 Gill博士（蛋白质核C）将指导病毒峰值蛋白，受体蛋白和抗体的合成和纯化，这对于每个项目必不可少。这项研究将有助于解释SARS-COV的起源，解释SARS的病理，开发针对SARS的候选疫苗和药物，并在SARS的新动物模型中对其进行测试。