Project 1

项目1

基本信息

批准号：
10270978
负责人：
Abraam M. Yakoub
金额：
$ 25.37万
依托单位：
UNIVERSITY OF NORTH DAKOTA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-13 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10270978
关键词：
2019-nCoV ACE2 American Animal Model Antiviral Agents Antiviral Therapy Applications Grants Area Basic Science Biochemical COVID-19 COVID-19 pathogenesis COVID-19 treatment Cells Centers of Research Excellence Cessation of life Collaborations Core Facility Country Disasters Disease Ensure FDA approved Faculty Fluorescence Foundations Future Genetic Models Goals Human Immune Immune response In Vitro Individual Infection Inflammatory Response Innate Immune Response Knowledge Libraries Measurement Mediating Methods Mission Molecular Molecular Genetics Mus Outcome Pathogenesis Pharmacotherapy Pneumonia Predisposition Public Health Reporter Reporting Research Research Project Grants Resources Respiratory Failure Role SARS-CoV-2 infection SARS-CoV-2 pathogenesis Severe Acute Respiratory Syndrome Severities Testing Therapeutic Intervention Tissues Tropism United States National Institutes of Health Vaccines Viral Viral Pathogenesis Virulence Virus Virus Diseases Virus Inhibitors Writing animal tissue base betacoronavirus drug candidate drug discovery effective therapy experience immunoregulation in vivo in vivo Model inhibitor/antagonist insight mouse model novel novel therapeutics pandemic disease pathogen receptor small molecule success synergism targeted treatment therapeutic evaluation therapy development tissue tropism viral entry inhibitor virology virus tropism

项目摘要

Summary Coronavirus Disease of 2019 (COVID-19) is a US and global public health crisis. It has led to the deaths of hundreds of thousands in the US and worldwide. COVID-19 is caused by a novel beta-coronavirus (CoV) known as Severe Acute Respiratory Syndrome (SARS)-CoV-2, which was reported to cause severe pneumonia and lethal respiratory failure. Little is known about the disease mechanism of this virus. Thus, animal models are urgently needed to start to investigate the SARS-CoV-2 pathogenesis mechanisms or test therapeutic interventions. In this application, we propose to establish the tissue tropism of SARS-CoV-2 in vivo by comparing two different mouse models that show moderate or severe disease in parallel. We also propose to test compound libraries to identify inhibitors of viral infection as drug candidates for COVID-19. We will also determine how the virus modulates innate immune responses in vivo in order to establish virulence. The proposed research will have manifold impact on the scientific battlefront on SARS-CoV-2 and the deadly COVID-19.

概括 2019 年冠状病毒病 (COVID-19) 是一场美国和全球公共卫生危机。它导致了以下人员的死亡美国和世界各地有数十万人。 COVID-19 是由一种新型 β 冠状病毒 (CoV) 引起的被称为严重急性呼吸系统综合症 (SARS)-CoV-2，据报道会导致严重肺炎和致命性呼吸衰竭。人们对这种病毒的致病机制知之甚少。因此，迫切需要动物模型开始研究SARS-CoV-2发病机制或进行测试治疗干预。在此应用中，我们建议建立 SARS-CoV-2 体内的组织向性通过比较同时显示中度或重度疾病的两种不同小鼠模型。我们还建议测试化合物库，以确定病毒感染抑制剂作为 COVID-19 的候选药物。我们也会确定病毒如何调节体内先天免疫反应以建立毒力。这拟议的研究将对 SARS-CoV-2 和致命病毒的科学战线产生多方面的影响新冠肺炎。