Berg, Hannes ; Wirtz Martin, Maria A. ; Altincekic, Nadide ; Alshamleh, Islam ; Kaur Bains, Jasleen ; Blechar, Julius ; Ceylan, Betül ; Jesus, Vanessa de ; Dhamotharan, Karthikeyan ; Fuks, Christin ; Gande, Santosh L. ; Hargittay, Bruno ; Hohmann, Katharina F. ; Hutchison, Marie T. ; Korn, Sophie Marianne ; Krishnathas, Robin ; Kutz, Felicitas ; Linhard, Verena ; Matzel, Tobias ; Meiser, Nathalie ; Niesteruk, Anna ; Pyper, Dennis J. ; Schulte, Linda ; Trucks, Sven ; Azzaoui, Kamal ; Blommers, Marcel J. J. ; Gadiya, Yojana ; Karki, Reagon ; Zaliani, Andrea ; Gribbon, Philip ; Silva Almeida, Marcius da ; Dinis Anobom, Cristiane ; Bula, Anna L. ; Bütikofer, Matthias ; Putinhon Caruso, Ícaro ; Caterina Felli, Isabella ; Da Poian, Andrea T. ; Cardoso de Amorim, Gisele ; Fourkiotis, Nikolaos K. ; Gallo, Angelo ; Ghosh, Dhiman ; Gomes‐Neto, Francisco ; Gorbatyuk, Oksana ; Hao, Bing ; Kurauskas, Vilius ; Lecoq, Lauriane ; Li, Yunfeng ; Cunha Mebus‐Antunes, Nathane ; Mompeán, Miguel ; Cristtina Neves‐Martins, Thais ; Ninot‐Pedrosa, Martí ; Pinheiro, Anderson S. ; Pontoriero, Letizia ; Pustovalova, Yulia ; Riek, Roland ; Robertson, Angus J. ; Jose Abi Saad, Marie ; Treviño, Miguel Á. ; Tsika, Aikaterini C. ; Almeida, Fabio C. L. ; Bax, Ad ; Henzler‐Wildman, Katherine ; Hoch, Jeffrey C. ; Jaudzems, Kristaps ; Laurents, Douglas V. ; Orts, Julien ; Pierattelli, Roberta ; Spyroulias, Georgios A. ; Duchardt‐Ferner, Elke ; Ferner, Jan ; Fürtig, Boris ; Hengesbach, Martin ; Löhr, Frank ; Qureshi, Nusrat ; Richter, Christian ; Saxena, Krishna ; Schlundt, Andreas ; Sreeramulu, Sridhar ; Wacker, Anna ; Weigand, Julia E. ; Wirmer‐Bartoschek, Julia ; Wöhnert, Jens ; Schwalbe, Harald (2022)
Comprehensive fragment screening of the SARS‐CoV‐2 proteome explores novel chemical space for drug development.
In: Angewandte Chemie International Edition, 61 (46)
doi: 10.1002/anie.202205858
Artikel, Bibliographie
Dies ist die neueste Version dieses Eintrags.
Kurzbeschreibung (Abstract)
SARS‐CoV‐2 (SCoV2) and its variants of concern pose serious challenges to the public health. The variants increased challenges to vaccines, thus necessitating for development of new intervention strategies including anti‐virals. Within the international Covid19‐NMR consortium, we have identified binders targeting the RNA genome of SCoV2. We established protocols for the production and NMR characterization of more than 80 % of all SCoV2 proteins. Here, we performed an NMR screening using a fragment library for binding to 25 SCoV2 proteins and identified hits also against previously unexplored SCoV2 proteins. Computational mapping was used to predict binding sites and identify functional moieties (chemotypes) of the ligands occupying these pockets. Striking consensus was observed between NMR‐detected binding sites of the main protease and the computational procedure. Our investigation provides novel structural and chemical space for structure‐based drug design against the SCoV2 proteome.
| Typ des Eintrags: | Artikel | ||||
|---|---|---|---|---|---|
| Erschienen: | 2022 | ||||
| Autor(en): | Berg, Hannes ; Wirtz Martin, Maria A. ; Altincekic, Nadide ; Alshamleh, Islam ; Kaur Bains, Jasleen ; Blechar, Julius ; Ceylan, Betül ; Jesus, Vanessa de ; Dhamotharan, Karthikeyan ; Fuks, Christin ; Gande, Santosh L. ; Hargittay, Bruno ; Hohmann, Katharina F. ; Hutchison, Marie T. ; Korn, Sophie Marianne ; Krishnathas, Robin ; Kutz, Felicitas ; Linhard, Verena ; Matzel, Tobias ; Meiser, Nathalie ; Niesteruk, Anna ; Pyper, Dennis J. ; Schulte, Linda ; Trucks, Sven ; Azzaoui, Kamal ; Blommers, Marcel J. J. ; Gadiya, Yojana ; Karki, Reagon ; Zaliani, Andrea ; Gribbon, Philip ; Silva Almeida, Marcius da ; Dinis Anobom, Cristiane ; Bula, Anna L. ; Bütikofer, Matthias ; Putinhon Caruso, Ícaro ; Caterina Felli, Isabella ; Da Poian, Andrea T. ; Cardoso de Amorim, Gisele ; Fourkiotis, Nikolaos K. ; Gallo, Angelo ; Ghosh, Dhiman ; Gomes‐Neto, Francisco ; Gorbatyuk, Oksana ; Hao, Bing ; Kurauskas, Vilius ; Lecoq, Lauriane ; Li, Yunfeng ; Cunha Mebus‐Antunes, Nathane ; Mompeán, Miguel ; Cristtina Neves‐Martins, Thais ; Ninot‐Pedrosa, Martí ; Pinheiro, Anderson S. ; Pontoriero, Letizia ; Pustovalova, Yulia ; Riek, Roland ; Robertson, Angus J. ; Jose Abi Saad, Marie ; Treviño, Miguel Á. ; Tsika, Aikaterini C. ; Almeida, Fabio C. L. ; Bax, Ad ; Henzler‐Wildman, Katherine ; Hoch, Jeffrey C. ; Jaudzems, Kristaps ; Laurents, Douglas V. ; Orts, Julien ; Pierattelli, Roberta ; Spyroulias, Georgios A. ; Duchardt‐Ferner, Elke ; Ferner, Jan ; Fürtig, Boris ; Hengesbach, Martin ; Löhr, Frank ; Qureshi, Nusrat ; Richter, Christian ; Saxena, Krishna ; Schlundt, Andreas ; Sreeramulu, Sridhar ; Wacker, Anna ; Weigand, Julia E. ; Wirmer‐Bartoschek, Julia ; Wöhnert, Jens ; Schwalbe, Harald | ||||
| Art des Eintrags: | Bibliographie | ||||
| Titel: | Comprehensive fragment screening of the SARS‐CoV‐2 proteome explores novel chemical space for drug development | ||||
| Sprache: | Englisch | ||||
| Publikationsjahr: | 2022 | ||||
| Ort: | Weinheim | ||||
| Verlag: | Wiley-VCH | ||||
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Angewandte Chemie International Edition | ||||
| Jahrgang/Volume einer Zeitschrift: | 61 | ||||
| (Heft-)Nummer: | 46 | ||||
| Kollation: | 12 Seiten | ||||
| DOI: | 10.1002/anie.202205858 | ||||
| Zugehörige Links: | |||||
| Kurzbeschreibung (Abstract): | SARS‐CoV‐2 (SCoV2) and its variants of concern pose serious challenges to the public health. The variants increased challenges to vaccines, thus necessitating for development of new intervention strategies including anti‐virals. Within the international Covid19‐NMR consortium, we have identified binders targeting the RNA genome of SCoV2. We established protocols for the production and NMR characterization of more than 80 % of all SCoV2 proteins. Here, we performed an NMR screening using a fragment library for binding to 25 SCoV2 proteins and identified hits also against previously unexplored SCoV2 proteins. Computational mapping was used to predict binding sites and identify functional moieties (chemotypes) of the ligands occupying these pockets. Striking consensus was observed between NMR‐detected binding sites of the main protease and the computational procedure. Our investigation provides novel structural and chemical space for structure‐based drug design against the SCoV2 proteome. |
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| Alternatives oder übersetztes Abstract: |
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| Freie Schlagworte: | COVID19-NMR, Drug Discovery, Fragment Screening, NMR Spectroscopy, Protein, SARS-CoV-2 | ||||
| ID-Nummer: | e202205858 | ||||
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 540 Chemie 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin, Gesundheit |
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| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > RNA Biochemie |
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| Hinterlegungsdatum: | 23 Jan 2024 08:04 | ||||
| Letzte Änderung: | 23 Jan 2024 08:04 | ||||
| PPN: | |||||
| Zugehörige Links: | |||||
| Export: | |||||
| Suche nach Titel in: | TUfind oder in Google | ||||
Verfügbare Versionen dieses Eintrags
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Comprehensive Fragment Screening of the SARS‐CoV‐2 Proteome Explores Novel Chemical Space for Drug Development. (deposited 22 Jan 2024 13:48)
- Comprehensive fragment screening of the SARS‐CoV‐2 proteome explores novel chemical space for drug development. (deposited 23 Jan 2024 08:04) [Gegenwärtig angezeigt]
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