Institute for Molecular Biosciences, Goethe-University Frankfurt, Max-von-Laue-Str. 9, 60438, Frankfurt/M., Germany.
Center for Biomolecular Magnetic Resonance (BMRZ), Goethe-University Frankfurt, Max-von-Laue-Str. 7, 60438, Frankfurt/M., Germany.
Biomol NMR Assign. 2021 Oct;15(2):335-340. doi: 10.1007/s12104-021-10026-7. Epub 2021 Apr 29.
The SARS-CoV-2 virus is the cause of the respiratory disease COVID-19. As of today, therapeutic interventions in severe COVID-19 cases are still not available as no effective therapeutics have been developed so far. Despite the ongoing development of a number of effective vaccines, therapeutics to fight the disease once it has been contracted will still be required. Promising targets for the development of antiviral agents against SARS-CoV-2 can be found in the viral RNA genome. The 5'- and 3'-genomic ends of the 30 kb SCoV-2 genome are highly conserved among Betacoronaviruses and contain structured RNA elements involved in the translation and replication of the viral genome. The 40 nucleotides (nt) long highly conserved stem-loop 4 (5_SL4) is located within the 5'-untranslated region (5'-UTR) important for viral replication. 5_SL4 features an extended stem structure disrupted by several pyrimidine mismatches and is capped by a pentaloop. Here, we report extensive H, C, N and P resonance assignments of 5_SL4 as the basis for in-depth structural and ligand screening studies by solution NMR spectroscopy.
SARS-CoV-2 病毒是导致呼吸道疾病 COVID-19 的病原体。截至目前，由于尚未开发出有效的治疗方法，严重 COVID-19 病例的治疗干预措施仍然不可用。尽管目前正在开发许多有效的疫苗，但一旦感染该病毒，仍将需要针对该疾病的治疗方法。针对 SARS-CoV-2 的抗病毒药物的开发有希望的靶点可以在病毒 RNA 基因组中找到。30kb SCoV-2 基因组的 5'和 3'基因组末端在β冠状病毒中高度保守，包含参与病毒基因组翻译和复制的结构 RNA 元件。40 个核苷酸（nt）长的高度保守茎环 4（5_SL4）位于对病毒复制很重要的 5'非翻译区（5'-UTR）内。5_SL4 具有延伸的茎结构，被几个嘧啶错配破坏，并由五聚体环封闭。在这里，我们报告了 5_SL4 的广泛 H、C、N 和 P 共振分配，作为通过溶液 NMR 光谱进行深入结构和配体筛选研究的基础。
