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

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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Wacker A,Weigand JE,Akabayov SR,Altincekic N,Bains JK,Banijamali E,Binas O,Castillo-Martinez J,Cetiner E,Ceylan B,Chiu LY,Davila-Calderon J,Dhamotharan K,Duchardt-Ferner E,Ferner J,Frydman L,Fürtig B,Gallego J,Grün JT

doi

10.1093/nar/gkaa1013

subject

Has Abstract

pub_date

2020-12-16 00:00:00

pages

12415-12435

issue

22

eissn

0305-1048

issn

1362-4962

pii

5961789

journal_volume

48

pub_type

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