Sridhar Sreeramulu, Christian Richter, Hannes Berg, Maria Alexandra Wirtz Martin, Betül Ceylan, Tobias Matzel, Jennifer Adam, Nadide Altınçekiç, Kamal Azzaoui, Jasleen Kaur Bains, Marcel Jules José Blommers, Jan Ferner, Boris Fürtig, Michael Göbel, J. Tassilo Grün, Martin Hengesbach, Katharina Felicitas Hohmann, Daniel Hymon, Božana Knežić, Jason N. Martins, Klara Rebecca Mertinkus, Anna Niesteruk, Stephen A. Peter, Dennis Joshua Pyper, Nusrat Qureshi, Ute Scheffer, Andreas Schlundt, Robbin Schnieders, Elke Stirnal, Alexey Sudakov, Alix Friederike Tröster, Jennifer Vögele, Anna Wacker, Julia Weigand, Julia Wirmer-Bartoschek, Jens Wöhnert, Harald Schwalbe
- 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.
MetadatenAuthor: | Sridhar SreeramuluORCiDGND, Christian RichterORCiDGND, Hannes Berg, Maria Alexandra Wirtz MartinORCiD, Betül CeylanGND, Tobias Matzel, Jennifer Adam, Nadide AltınçekiçORCiDGND, Kamal Azzaoui, Jasleen Kaur BainsORCiDGND, Marcel Jules José Blommers, Jan FernerORCiDGND, Boris FürtigORCiDGND, Michael GöbelORCiDGND, J. Tassilo GrünORCiDGND, Martin HengesbachORCiDGND, Katharina Felicitas HohmannGND, Daniel Hymon, Božana KnežićGND, Jason N. Martins, Klara Rebecca MertinkusORCiD, Anna NiesterukGND, Stephen A. PeterGND, Dennis Joshua Pyper, Nusrat QureshiORCiDGND, Ute Scheffer, Andreas SchlundtORCiDGND, Robbin SchniedersGND, Elke Stirnal, Alexey Sudakov, Alix Friederike TrösterGND, Jennifer VögeleORCiD, Anna WackerORCiDGND, Julia WeigandORCiDGND, Julia Wirmer-BartoschekORCiD, Jens WöhnertORCiDGND, Harald SchwalbeORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-639288 |
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DOI: | https://doi.org/10.1002/anie.202103693 |
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ISSN: | 1521-3773 |
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Parent Title (English): | Angewandte Chemie |
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Publisher: | Wiley-VCH |
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Place of publication: | Weinheim |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2021/06/23 |
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Date of first Publication: | 2021/06/23 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2022/04/05 |
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Tag: | Covid19-nmr; NMR spectroscopy; RNA; SARS-CoV-2; fragment screening |
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Volume: | 60 |
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Issue: | 35 |
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Page Number: | 10 |
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First Page: | 19191 |
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Last Page: | 19200 |
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Note: | 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. |
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HeBIS-PPN: | 493370625 |
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Institutes: | Biochemie, Chemie und Pharmazie |
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| Wissenschaftliche Zentren und koordinierte Programme / Zentrum für Biomolekulare Magnetische Resonanz (BMRZ) |
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Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
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| 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
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| 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung 4.0 |
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