Multi-dimensional comparison of differentially pathogenic coronaviruses (CoV) in human lung tissue

人肺组织中差异致病性冠状病毒（CoV）的多维度比较

基本信息

批准号：
10377826
负责人：
Jeffrey R Johnson
金额：
$ 25.38万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-24 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10377826
关键词：
2019-nCoV Autopsy COVID-19 COVID-19 pandemic COVID-19 patient COVID-19 therapeutics COVID-19 treatment Cell Line Cells Cessation of life China Complex Coronavirus Coronavirus Infections Country Data Development Disease Disease Outbreaks Disease Outcome Environment Enzyme-Linked Immunosorbent Assay Event FDA approved Genomics Human Immune response Immunologics Immunophenotyping Infection Inflammation Inflammatory Inflammatory Response Kinetics Lower respiratory tract structure Lung Lung diseases Mass Spectrum Analysis Mediating Middle East Respiratory Syndrome Modeling Pathogenesis Pathogenicity Pathology Pathway interactions Phosphorylation Pneumonia Predisposition Proteins Proteome Proteomics RNA Viruses Reporting SARS-CoV-2 infection Severe Acute Respiratory Syndrome Structure of parenchyma of lung System Technology Testing Therapeutic Tissues Virus Virus Diseases Virus Replication base cell type human coronavirus in vivo new therapeutic target novel novel coronavirus pandemic disease phosphoproteomics respiratory pathogen small molecule inhibitor therapeutic development virus host interaction

项目摘要

PROJECT SUMMARY: SARS-CoV-2 is a novel coronavirus and the cause of the current global pandemic. This outbreak started in December of 2019 and has now spread over the entire world. SARS-CoV-2 is a respiratory pathogen that causes COVID-19, which has been the cause of more than 2.6 million deaths worldwide, with over 538,000 deaths in the US alone as of March 2021. The primary pathology caused by SARS-CoV-2 infection in humans is in the lungs. In this proposal, we seek to study the early events following coronavirus infection by infecting human lung tissue ex vivo. In order to understand the mechanism by which SARS-CoV-2 causes such severe disease outcomes, we will compare two coronavirus strains, SARS-CoV-2 (which is highly pathogenic) and NL63 (which is mildly pathogenic) in humans. In Aim 1, we will identify differences in viral replication kinetics, infected cell types, and the inflammatory response. In Aim 2, we will characterize the host response to infection using mass spectrometry-based proteomics. Understanding these complex virus:host components in a human system and how these differ between coronaviruses will lead to new hypotheses for in vivo susceptibility and identify new drug targets for therapeutic development.

项目概要： SARS-CoV-2 是一种新型冠状病毒，也是当前全球大流行的原因。此次疫情爆发始于 2019 年 12 月，现已遍布全球。 SARS-CoV-2 是一种呼吸道病原体，导致全球 260 万人死亡，其中 538,000 人死亡截至 2021 年 3 月，仅美国就有死亡病例。人类感染 SARS-CoV-2 引起的主要病理学是在肺部。在本提案中，我们寻求通过感染冠状病毒来研究冠状病毒感染后的早期事件离体人体肺组织。为了了解 SARS-CoV-2 造成如此严重后果的机制疾病结果，我们将比较两种冠状病毒株：SARS-CoV-2（具有高致病性）和 NL63（具有轻度致病性）对人类。在目标 1 中，我们将确定病毒复制动力学的差异，感染细胞类型和炎症反应。在目标 2 中，我们将描述宿主对感染的反应使用基于质谱的蛋白质组学。了解这些复杂的病毒：人体的宿主成分系统以及冠状病毒之间的差异将导致体内易感性的新假设确定治疗开发的新药物靶点。