Project 1

项目1

• 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
• 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

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.

摘要 2019年冠状病毒病(新冠肺炎)是美国和全球的公共卫生危机。它已经导致了许多人的死亡 在美国和世界各地有数十万人。新冠肺炎是由一种新型的贝塔冠状病毒引起的 被称为严重急性呼吸综合征(SARS)-CoV-2，据报道会导致严重的 肺炎和致命的呼吸衰竭。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的致病机制或检测 治疗性干预。在这一应用中，我们建议在体内建立SARS-CoV-2的组织趋向性 通过比较两种不同的平行显示中度或严重疾病的小鼠模型。我们还提议 测试化合物文库，以确定病毒感染抑制剂作为新冠肺炎的候选药物。我们还将 确定病毒如何调节体内的先天免疫反应，以建立毒力。这个 拟议的研究将对SARS-CoV-2和致命的 新冠肺炎。