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Exploring the Druggability of Conserved RNA Regulatory Elements in the SARS-CoV-2 Genome.
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.
  • Sreeramulu S; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Richter C; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Berg H; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Wirtz Martin MA; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Ceylan B; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Matzel T; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Adam J; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Altincekic N; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Azzaoui K; Saverna Therapeutics, Pumpmattenweg 3, 4105, Biel-Benken, Switzerland.
  • Bains JK; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Blommers MJJ; Saverna Therapeutics, Pumpmattenweg 3, 4105, Biel-Benken, Switzerland.
  • Ferner J; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Fürtig B; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Göbel M; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Grün JT; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Hengesbach M; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Hohmann KF; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Hymon D; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Knezic B; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Martins JN; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Mertinkus KR; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Niesteruk A; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Peter SA; Department of Biology, Technical University of Darmstadt, Schnittspahnstr. 10, 64287, Darmstadt, Germany.
  • Pyper DJ; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Qureshi NS; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Scheffer U; Present address: EMBL Heidelberg, Meyerhofstr. 1, 69117, Heidelberg, Germany.
  • Schlundt A; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Schnieders R; Institute for Molecular Biosciences, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Stirnal E; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Sudakov A; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Tröster A; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Vögele J; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Wacker A; Institute for Molecular Biosciences, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Weigand JE; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Wirmer-Bartoschek J; Department of Biology, Technical University of Darmstadt, Schnittspahnstr. 10, 64287, Darmstadt, Germany.
  • Wöhnert J; Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
  • Schwalbe H; Institute for Molecular Biosciences, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7+9, 60438, Frankfurt/M., Germany.
Angew Chem Int Ed Engl ; 60(35): 19191-19200, 2021 08 23.
Article in English | MEDLINE | ID: covidwho-1279344
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA, Viral / Genome / Small Molecule Libraries / SARS-CoV-2 Type of study: Randomized controlled trials Topics: Traditional medicine Language: English Journal: Angew Chem Int Ed Engl Year: 2021 Document Type: Article Affiliation country: Anie.202103693

Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA, Viral / Genome / Small Molecule Libraries / SARS-CoV-2 Type of study: Randomized controlled trials Topics: Traditional medicine Language: English Journal: Angew Chem Int Ed Engl Year: 2021 Document Type: Article Affiliation country: Anie.202103693