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Exploring the Druggability of Conserved RNA Regulatory Elements in the SARS‐CoV‐2 Genome
Author(s) -
Sreeramulu Sridhar,
Richter Christian,
Berg Hannes,
Wirtz Martin Maria A.,
Ceylan Betül,
Matzel Tobias,
Adam Jennifer,
Altincekic Nadide,
Azzaoui Kamal,
Bains Jasleen Kaur,
Blommers Marcel J. J.,
Ferner Jan,
Fürtig Boris,
Göbel Michael,
Grün J. Tassilo,
Hengesbach Martin,
Hohmann Katharina F.,
Hymon Daniel,
Knezic Bozana,
Martins Jason N.,
Mertinkus Klara R.,
Niesteruk Anna,
Peter Stephen A.,
Pyper Dennis J.,
Qureshi Nusrat S.,
Scheffer Ute,
Schlundt Andreas,
Schnieders Robbin,
Stirnal Elke,
Sudakov Alexey,
Tröster Alix,
Vögele Jennifer,
Wacker Anna,
Weigand Julia E.,
WirmerBartoschek Julia,
Wöhnert Jens,
Schwalbe Harald
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202103693
Subject(s) - druggability , rna , computational biology , riboswitch , genome , biology , genetics , nucleic acid structure , nucleotide , base pair , binding site , non coding rna , gene
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 1 H‐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.