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.

SARS-COV-2（SCOV-2）在全球范围内的快速且几乎不受限制地扩散造成的持续的共证，这是对进行病毒蛋白和RNA进行协调投资的全球范围内，以实现抗病毒药的快速发展。我们使用基于NMR的结构生物学来研究SCOV-2的整个基因组RNA，尤其是在其5'-和3'-非翻译区域（UTRS）中发现的结构化元件。 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相关冠状病毒之间的保守及其结构具有生物学意义。基于这些发现，我们提出了一种“分裂和诱因”方法，其中溶液中的NMR-SpectRoscopicy可以提供有关其结构和动态的高分辨率信息。我们的项目分为三个不同的目标。目标1的重点是非传统RNA元素的详细表征。这些元素的RNA结构和动力学通常偏离标准的RNA结构，并且这些元素可以充当与其他RNA，蛋白质和潜在病毒传播抑制剂的相互作用中心。目标2专注于SCOV-2中的关键复制元件5_SL5。我们旨在确定5_SL5中各个元素的结构和动力学，并通过NMR和SAXS方法的结合重建整个RNA架构。在目标3中，我们将重点关注SCOV -2中-1移码区域的结构和动态特征的投资。