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

• DOI: 10.1002/ange.202103693
• Publication Date: 2021-06-23T18:09:31Z
• Authors: Sridhar Sreeramulu; Christian Richter; Hannes Berg; Maria A. Wirtz Ma...; Betül Ceylan; Tobias Matzel; Jennifer Adam; Nadide Altincekic; Kamal Azzaoui; Jasleen Kaur Bains; Marcel J. J. Blom...; Jan Ferner; Boris Fürtig; Michael Göbel; J. Tassilo Grün; Martin Hengesbach; Katharina F. Hohmann; Daniel Hymon; Bozana Knezic; Jason N. Martins; Klara R. Mertinkus; Anna Niesteruk; Stephen A. Peter; Dennis J. Pyper; Nusrat S. Qureshi; Ute Scheffer; Andreas Schlundt; Robbin Schnieders; Elke Stirnal; Alexey Sudakov; Alix Tröster; Jennifer Vögele; Anna Wacker; Julia E. Weigand; Julia Wirmer‐Bart...; Jens Wöhnert; Harald Schwalbe
• Keywords: Druggability; Riboswitch; Nucleic acid structure

Abstract SARS‐CoV‐2 contains a positive single‐stranded RNA genome of approximately 30 000 nucleotides. Within this genome, 15 elements were identified as conserved between SARS‐CoV and SARS‐CoV‐2. By nuclear magnetic resonance (NMR) spectroscopy, we previously determined that these fold independently, in line with data from vivo ex‐vivo structural probing experiments. These contain non‐base‐paired regions potentially harbor ligand‐binding pockets. Here, performed an NMR‐based screening poised fragment library 768 compounds for binding to RNAs, employing three different 1 H‐based 1D NMR assays. The common well RNA‐element specific hits. results allow selection the most promising putative drug targets. Based on hits, derive key functional units groups ligands effective targeting