1H, 13C, 15N and 31P chemical shift assignment for stem-loop 4 from the 5\u2032-UTR of SARS-CoV-2

Jennifer Vögele,J Tassilo Grün,Boris Fürtig,Frank Löhr,Jens Wöhnert,Betül Ceylan,Katharina F Hohmann,Stephen A Peter,Jasleen Kaur Bains,Julia E Weigand,Anna Wacker,Martin Hengesbach,Christian Richter,Alexey Sudakov,Andreas Schlundt,Elke Stirnal,Daniel Hymon,Dennis J Pyper ,Božana Knezic ,Harald Schwalbe,Jan Ferner ,Julia Wirmer‐Bartoschek ,Nusrat Shahin Qureshi ,Nadide Altincekic,Elke Duchardt‐Ferner

doi:10.1007/s12104-021-10026-7

Jennifer Vögele, J Tassilo Grün + Show 23 more

Open Access

https://doi.org/10.1007/s12104-021-10026-7

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Abstract

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 1H, 13C, 15N and 31P resonance assignments of 5_SL4 as the basis for in-depth structural and ligand screening studies by solution NMR spectroscopy.

Highlights

SARS-CoV-2 is a human Betacoronavirus which causes the severe acute respiratory syndrome COVID-19
Efforts aiming at the development of new antiviral agents against SARS-CoV-2 have been largely restricted to studies of the viral proteins, leaving the potentially vast reservoir of putative drug-targets to be found in the structured, conserved and functional genomic RNA elements essentially untapped
As a starting point of the initiative, the individual structured elements of the SARSCoV-2 genome were subjected to high resolution structure determination by NMR spectroscopy in a ‘divideand-conquer’ approach

Summary

Introduction

SARS-CoV-2 is a human Betacoronavirus which causes the severe acute respiratory syndrome COVID-19. 2 Center for Biomolecular Magnetic Resonance (BMRZ), Goethe-University Frankfurt, Max‐von‐Laue‐Str. 7, 60438 The 5′- region (Fig. 1a) of the SARS-CoV-2 genome consists of eight stem-loop (SL) structures.

Results

Conclusion