Details

Autor(en) / Beteiligte

• 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.
• Wirmer‐Bartoschek, Julia
• Wöhnert, Jens
• Schwalbe, Harald

Titel

Exploring the Druggability of Conserved RNA Regulatory Elements in the SARS‐CoV‐2 Genome

Ist Teil von

• Angewandte Chemie, 2021-08, Vol.133 (35), p.19340-19349

Ort / Verlag

Weinheim: Wiley Subscription Services, Inc

Erscheinungsjahr

2021

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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. The RNA genome of SARS‐CoV‐2 contains 15 independently folded regulatory RNA elements. By NMR‐based fragment screening, the RNA target space for small molecule binding, functional mapping and inhibition is defined.