Dissecting the peptide motifs controlling coronavirus infections

剖析控制冠状病毒感染的肽基序

基本信息

批准号：
10648391
负责人：
Thomas Miller Gallagher
金额：
$ 22.23万
依托单位：
LOYOLA UNIVERSITY CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-10 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10648391
关键词：
Affect Antiviral Agents Binding Biochemical COVID-19 vaccine Cell membrane Cell surface Cells Cellular Structures Coat Protein Complex I Code Communication Complex Coronavirus Coronavirus Infections Cytoplasm Cytoplasmic Tail Data E protein Endoplasmic Reticulum Endosomes Foundations Goals Human Infection Integration Host Factors Knowledge Laboratories Membrane Membrane Proteins Methods Molecular Chaperones Mus Organelles Pathogenicity Pathway interactions Peptides Process Proteins Recombinants Recycling Research Site System Vesicle Viral Viral Matrix Proteins Viral Proteins Virion Virus Virus Diseases Virus-like particle comparative improved intracellular protein transport knockout gene novel coronavirus particle pharmacologic protein transport recombinant virus sorting nexins trafficking vesicle transport virus host interaction

项目摘要

PROJECT SUMMARY/ABSTRACT This proposal aims to evaluate coronavirus assembly and egress. These late infection stages are understudied relative to coronavirus entry replication. Additional research is necessary to reveal how host cell machineries facilitate assembly and egress. Therefore, this proposal specifically focuses on coronavirus membrane proteins, their interactions with host cell components, and the relevance of these contacts to efficient virion formation and emergence from infected cells. Guided by biochemical and protein structural data documenting interfaces between viral peptide motifs and host coatomer and retromer complexes, we will construct recombinant murine coronaviruses and corona virus‐like particles with alternative motifs. Comparisons of recombinant virus infections, along with reductionist approaches assessing the formation and subcellular transport of virus‐like particles, will reveal how coatomer and retromer‐sorting nexins operate in controlling viral membrane protein trafficking, virus particle formation, and particle egress pathways. By expanding the studies to human pathogenic coronaviruses, we expect to identify commonly utilized host machineries that might be targeted by antiviral therapeutics.

项目概要/摘要该提案旨在评估冠状病毒的组装和流出。与冠状病毒进入复制相关的研究不足，需要进行更多研究。揭示宿主细胞机器如何促进组装和排出因此，该提案。特别关注冠状病毒膜蛋白及其与宿主细胞的相互作用组成部分，以及这些接触与有效病毒体形成和出现的相关性来自受感染细胞的生化和蛋白质结构数据文档界面引导。在病毒肽基序与宿主衣壳异构体和逆转录异构体复合物之间，我们将构建重组鼠冠状病毒和具有替代基序的冠状病毒样颗粒。重组病毒感染的比较以及评估感染的简化方法病毒样颗粒的形成和亚细胞运输，将揭示涂层异构体和逆转录酶分选连接蛋白可控制病毒膜蛋白运输、病毒颗粒通过将研究扩展到人类致病性。冠状病毒，我们希望识别出常用的主机，这些主机可能是抗病毒治疗的目标。