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.

项目摘要/摘要该建议旨在评估冠状病毒组装和出口。这些晚期感染阶段是相对于冠状病毒进入复制进行了研究。需要进行其他研究揭示宿主细胞机器如何促进组装和出口。因此，这个建议特别专注于冠状病毒膜蛋白，它们与宿主细胞的相互作用组件，以及这些接触与有效的病毒体形成和出现的相关性来自感染的细胞。在生化和蛋白质结构数据记录界面的指导下在病毒肽基序和宿主夹具和缩回络合物之间，我们将构建重组鼠冠状病毒和带有替代基序的类似电晕病毒的颗粒。重组病毒感染的比较，以及评估的还原主义方法类似病毒的颗粒的形成和亚细胞运输将揭示夹具和反缩回替代Nexins在控制病毒膜蛋白运输，病毒颗粒方面起作用形成和粒子出口途径。通过将研究扩展到人类的致病性冠状病毒，我们期望识别可能是常见的主机机器由抗病毒疗法靶向。