SARS-CoV-2-RNA: Understanding the RNA architecture of SARS-CoV-2

SARS-CoV-2 RNA：了解 SARS-CoV-2 的 RNA 结构

• 批准号: 495006306
• 负责人: Professor Dr. Harald Schwalbe
• 金额: --
• 依托单位: Institut für Organische Chemie und Chemische Biologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/495006306?language=en
• 关键词: SARS; CoV; RNA; Understanding; architecture

The ongoing COVID-19 pandemic caused by the rapid and almost unmitigated spread of SARS-CoV-2 (SCoV-2) across the world necessitates the coordinated investigation of its viral proteins and RNAs to enable the rapid development of antiviral drugs. We use NMR-based structural biology to investigate structured elements found throughout the genomic RNA of SCoV-2 and in particular in its 5’- and 3’-untranslated regions (UTRs). Current biochemical RNA structure probing tools so far used on the SCoV-2 RNA are intrinsically unable to define the structural and dynamic features of the non-canonical bulge and loop regions of the structured RNA-elements in the SCoV-2 genome but revealed (i) that the structural elements in the genomic RNA are organized in a modular fashion with local structured elements connected by single-stranded regions, (ii) that they are conserved between related coronaviruses and thus their structure is of biological significance. Based on these findings, we propose a ‘divide-and-conquer’ approach where NMR-spectroscopy in solution can provide high-resolution information about their structure and dynamics. Our project is divided into three different objectives. Objective 1 is focussed on the detailed characterization of non-canonical RNA elements. The RNA structure and dynamics of these elements typically deviates from standard RNA structure and primes these elements to function as interaction hubs with other RNAs, proteins and potential inhibitors of viral propagation. Objective 2 focusses on the key replication element 5_SL5 in SCoV-2. We aim to determine the structure and dynamics of individual elements within 5_SL5 as well as reconstruct the entire RNA architecture by a combination of NMR and SAXS approaches. In Objective 3, we will focus on the investigation of structural and dynamic features of the -1 frameshift region in SCoV-2.

由 SARS-CoV-2 (SCoV-2) 在全球范围内迅速且几乎毫无缓解的传播引起的持续的 COVID-19 大流行需要对其病毒蛋白和 RNA 进行协调研究，以实现抗病毒药物的快速开发。基于结构生物学来研究 SCoV-2 基因组 RNA 中发现的结构元件，特别是目前使用的生化 RNA 结构探测工具。关于 SCoV-2 RNA 的研究本质上无法定义 SCoV-2 基因组中结构化 RNA 元件的非规范凸起​​和环区域的结构和动态特征，但揭示 (i) 基因组 RNA 中的结构元件以模块化方式组织，局部结构元件通过单链区域连接，（ii）它们在相关冠状病毒之间是保守的，因此它们的结构具有生物学意义。基于这些发现，我们提出了“分而治之”的方法。 ' 接近哪里溶液中的核磁共振波谱可以提供有关其结构和动力学的高分辨率信息，我们的项目分为三个不同的目标，重点是非规范 RNA 元件的详细表征。我们的目标是从标准 RNA 结构中分离出这些元件，使其充当与其他 RNA、蛋白质和潜在病毒传播抑制剂的相互作用中心。确定 5_SL5 中各个元件的结构和动态，并通过 NMR 和 SAXS 方法的组合重建整个 RNA 结构。在目标 3 中，我们将重点研究 5_SL5 中 -1 移码区域的结构和动态特征。 SCoV-2。