TY  - JOUR
A1  - Sreeramulu, Sridhar
A1  - Richter, Christian
A1  - Berg, Hannes
A1  - Wirtz Martin, Maria Alexandra
A1  - Ceylan, Betül
A1  - Matzel, Tobias
A1  - Adam, Jennifer
A1  - Altınçekiç, Nadide
A1  - Azzaoui, Kamal
A1  - Bains, Jasleen Kaur
A1  - Blommers, Marcel Jules José
A1  - Ferner, Jan
A1  - Fürtig, Boris
A1  - Göbel, Michael
A1  - Grün, J. Tassilo
A1  - Hengesbach, Martin
A1  - Hohmann, Katharina Felicitas
A1  - Hymon, Daniel
A1  - Knežić, Božana
A1  - Martins, Jason N.
A1  - Mertinkus, Klara Rebecca
A1  - Niesteruk, Anna
A1  - Peter, Stephen A.
A1  - Pyper, Dennis Joshua
A1  - Qureshi, Nusrat
A1  - Scheffer, Ute
A1  - Schlundt, Andreas
A1  - Schnieders, Robbin
A1  - Stirnal, Elke
A1  - Sudakov, Alexey
A1  - Tröster, Alix Friederike
A1  - Vögele, Jennifer
A1  - Wacker, Anna
A1  - Weigand, Julia
A1  - Wirmer-Bartoschek, Julia
A1  - Wöhnert, Jens
A1  - Schwalbe, Harald
T1  - Exploring the druggability of conserved RNA regulatory elements in the SARS-CoV-2 genome
T2  - Angewandte Chemie
N2  - SARS-CoV-2 contains a positive single-stranded RNA genome of approximately 30 000 nucleotides. Within this genome, 15 RNA elements were identified as conserved between SARS-CoV and SARS-CoV-2. By nuclear magnetic resonance (NMR) spectroscopy, we previously determined that these elements fold independently, in line with data from in vivo and ex-vivo structural probing experiments. These elements contain non-base-paired regions that potentially harbor ligand-binding pockets. Here, we performed an NMR-based screening of a poised fragment library of 768 compounds for binding to these RNAs, employing three different 1H-based 1D NMR binding assays. The screening identified common as well as RNA-element specific hits. The results allow selection of the most promising of the 15 RNA elements as putative drug targets. Based on the identified hits, we derive key functional units and groups in ligands for effective targeting of the RNA of SARS-CoV-2.
KW  - Covid19-nmr
KW  - fragment screening
KW  - NMR spectroscopy
KW  - RNA
KW  - SARS-CoV-2
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63928
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-639288
SN  - 1521-3773
N1  - The work has been conducted in the international consortium of Covid19-NMR (covid19-nmr.de). Work at BMRZ is supported by the state of Hesse. Work in Covid19-nmr was supported by the Goethe Corona Funds, by the IWB-EFRE-program 20007375 of state of Hesse, the DFG through CRC902: “Molecular Principles of RNA-based regulation.” and through infrastructure funds (project numbers: 277478796, 277479031, 392682309, 452632086, 70653611) and by European Union's Horizon 2020 research and innovation program iNEXT-discovery under grant agreement No 871037. We thank Peter Maas (SPECS) for providing the compound D01 as a kind gift. Open access funding enabled and organized by Projekt DEAL.
VL  - 60
IS  - 35
SP  - 19191
EP  - 19200
PB  - Wiley-VCH
CY  - Weinheim
ER  -