Crosstalk between nonstructural proteins of SARS-CoV-2 and the autophagy signaling machinery

SARS-CoV-2 非结构蛋白与自噬信号机制之间的串扰

• 批准号: 458684168
• 负责人: Professor Dr. Björn Stork
• 金额: --
• 依托单位: Institut für Molekulare Medizin I
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2021
• 资助国家: 德国
• 起止时间: 2020-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/458684168?language=en
• 关键词: Crosstalk; between; nonstructural; proteins; SARS

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative virus of the coronavirus disease 2019 (COVID-19). Current medicinal research focuses on vaccine development and the identification of potential therapeutic targets. (Macro-)Autophagy is an intracellular degradation process responsible for the recycling of long-lived or damaged proteins and organelles. Importantly, coronavirus infection and autophagy rely on remodelling of intracellular membranes, i.e. the formation of replication organelles such as double-membrane vesicles by coronaviruses and the biogenesis of autophagosomes during autophagy. However, the involvement of autophagy-essential proteins such as components of the ULK1 complex or the class III PtdIns3K complex for the formation of SARS-CoV-2-induced double-membrane vesicles remains unclear. In this project, we aim at characterizing the crosstalk between nonstructural proteins of SARS-CoV-2 and the autophagy-inducing ULK1 and PtdIns3K complexes. Collectively, we want to identify pharmacological approaches that might point the way towards novel COVID-19 therapies.

严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是2019冠状病毒病（COVID-19）的致病病毒。目前的医学研究集中在疫苗开发和潜在治疗靶点的鉴定上。自噬是一种细胞内降解过程，负责回收长寿命或受损的蛋白质和细胞器。重要的是，冠状病毒感染和自噬依赖于细胞内膜的重塑，即冠状病毒形成复制细胞器如双膜囊泡和自噬过程中自噬体的生物发生。然而，自噬必需蛋白质，如ULK 1复合物或III类PtdIns 3 K复合物的组分参与SARS-CoV-2诱导的双膜囊泡的形成仍不清楚。在这个项目中，我们的目标是表征SARS冠状病毒-2的非结构蛋白和自噬诱导ULK 1和PtdIns 3 K复合物之间的串扰。总的来说，我们希望确定可能为新型COVID-19疗法指明方向的药理学方法。