Secondary structure determination of conserved SARS-CoV-2 RNA elements by NMR spectroscopy

Anna Wacker, Julia E Weigand, Sabine R Akabayov, Nadide Altincekic, Jasleen Kaur Bains, Elnaz Banijamali, Oliver Binas, Jesus Castillo-Martinez, Erhan Cetiner, Betül Ceylan, Liang-Yuan Chiu, Jesse Davila-Calderon, Karthikeyan Dhamotharan, Elke Duchardt-Ferner, Jan Ferner, Lucio Frydman, Boris Fürtig, José Gallego, J Tassilo Grün, Carolin Hacker, Christina Haddad, Martin Hähnke, Martin Hengesbach, Fabian Hiller, Katharina F Hohmann, Daniel Hymon, Vanessa de Jesus, Henry Jonker, Heiko Keller, Bozana Knezic, Tom Landgraf, Frank Löhr, Le Luo, Klara R Mertinkus, Christina Muhs, Mihajlo Novakovic, Andreas Oxenfarth, Martina Palomino-Schätzlein, Katja Petzold, Stephen A Peter, Dennis J Pyper, Nusrat S Qureshi, Magdalena Riad, Christian Richter, Krishna Saxena, Tatjana Schamber, Tali Scherf, Judith Schlagnitweit, Andreas Schlundt, Robbin Schnieders, Harald Schwalbe, Alvaro Simba-Lahuasi, Sridhar Sreeramulu, Elke Stirnal, Alexey Sudakov, Jan-Niklas Tants, Blanton S Tolbert, Jennifer Vögele, Lena Weiß, Julia Wirmer-Bartoschek, Maria A Wirtz Martin, Jens Wöhnert, and Heidi Zetzsche

Nucleic Acids Research, Volume 48, Issue 22, 16 December 2020, Pages 12415–12435

The pandemic caused by SARS-CoV-2 (SCoV2) highlights the need for coordinated research to combat COVID-19. A particularly important aspect is the development of medication. In addition to viral proteins, structured RNA elements represent a potent alternative as drug targets. The search for drugs that target RNA requires their high-resolution structural characterization. Using NMR spectroscopy, a worldwide consortium of NMR researchers aims to characterize potential RNA drug targets of SCoV2. This study reports the characterization of 15 conserved RNA elements located at the 5′ end, the ribosomal frameshift segment and the 3′-untranslated region of the SCoV2 genome, their large-scale production and NMR-based secondary structure determination. The NMR data reported here provide the basis for NMR investigations of RNA function, RNA interactions with viral and host proteins and screening campaigns to identify potential RNA binders for pharmaceutical intervention.

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