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

Author:

Wacker Anna1,Weigand Julia E2ORCID,Akabayov Sabine R3,Altincekic Nadide1,Bains Jasleen Kaur1,Banijamali Elnaz4,Binas Oliver1,Castillo-Martinez Jesus5,Cetiner Erhan1,Ceylan Betül1,Chiu Liang-Yuan6,Davila-Calderon Jesse6,Dhamotharan Karthikeyan7,Duchardt-Ferner Elke7,Ferner Jan1,Frydman Lucio3,Fürtig Boris1ORCID,Gallego José5ORCID,Grün J Tassilo1,Hacker Carolin8,Haddad Christina6,Hähnke Martin8,Hengesbach Martin1ORCID,Hiller Fabian8,Hohmann Katharina F1,Hymon Daniel1,de Jesus Vanessa1,Jonker Henry1,Keller Heiko7,Knezic Bozana1,Landgraf Tom1,Löhr Frank9,Luo Le4,Mertinkus Klara R1,Muhs Christina1,Novakovic Mihajlo3,Oxenfarth Andreas1,Palomino-Schätzlein Martina5,Petzold Katja4,Peter Stephen A2,Pyper Dennis J1,Qureshi Nusrat S1,Riad Magdalena4,Richter Christian1,Saxena Krishna1,Schamber Tatjana1,Scherf Tali3,Schlagnitweit Judith4,Schlundt Andreas7ORCID,Schnieders Robbin1,Schwalbe Harald1ORCID,Simba-Lahuasi Alvaro5,Sreeramulu Sridhar1,Stirnal Elke1,Sudakov Alexey1,Tants Jan-Niklas7,Tolbert Blanton S6,Vögele Jennifer7,Weiß Lena7,Wirmer-Bartoschek Julia1,Wirtz Martin Maria A1,Wöhnert Jens7ORCID,Zetzsche Heidi1

Affiliation:

1. Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany

2. Department of Biology, Technical University of Darmstadt, Schnittspahnstrasse 10, 64287 Darmstadt, Germany

3. Faculty of Chemistry, Weizmann Institute of Science, 7610001 Rehovot, Israel

4. Department of Medical Biochemistry and Biophysics, Karolinska Institute, Biomedicum 9B, Solnavägen 9, 17177 Stockholm, Sweden

5. School of Medicine, Catholic University of Valencia, C/Quevedo 2, 46001 Valencia, Spain

6. Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106, USA

7. Institute for Molecular Biosciences

8. Signals GmbH & Co. KG, Graf-von-Stauffenberg-Allee 83, 60438 Frankfurt/M, Germany

9. Institute of Biophysical Chemistry, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University Frankfurt, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany

Abstract

Abstract The current pandemic situation caused by the Betacoronavirus 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 nuclear magnetic resonance (NMR) spectroscopy, a worldwide consortium of NMR researchers aims to characterize potential RNA drug targets of SCoV2. Here, we report the characterization of 15 conserved RNA elements located at the 5′ end, the ribosomal frameshift segment and the 3′-untranslated region (3′-UTR) of the SCoV2 genome, their large-scale production and NMR-based secondary structure determination. The NMR data are corroborated with secondary structure probing by DMS footprinting experiments. The close agreement of NMR secondary structure determination of isolated RNA elements with DMS footprinting and NMR performed on larger RNA regions shows that the secondary structure elements fold independently. 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.

Funder

Goethe University

Deutsche Forschungsgemeinschaft

National Institutes of Health

Horizon 2020

Weizmann′s Internal Coronavirus Fund

German-Israel Foundation

Ministerio de Economía y Competitividad

la Caixa Banking Foundation

Catholic University of Valencia

Hessisches Ministerium für Wissenschaft und Kunst

iNEXT-Discovery

Publisher

Oxford University Press (OUP)

Subject

Genetics

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