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 (2024)
Comprehensive Fragment Screening of the SARS‐CoV‐2 Proteome Explores Novel Chemical Space for Drug Development.
In: Angewandte Chemie International Edition, 2022, 61 (46)
doi: 10.26083/tuprints-00022910
Artikel, Zweitveröffentlichung, Verlagsversion

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:	2024
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:	Zweitveröffentlichung
Titel:	Comprehensive Fragment Screening of the SARS‐CoV‐2 Proteome Explores Novel Chemical Space for Drug Development
Sprache:	Englisch
Publikationsjahr:	22 Januar 2024
Ort:	Darmstadt
Publikationsdatum der Erstveröffentlichung:	2022
Ort der Erstveröffentlichung:	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:	10.26083/tuprints-00022910
URL / URN:	https://tuprints.ulb.tu-darmstadt.de/22910
Zugehörige Links:	Forschungsdaten https://doi.org/10.1002/anie.202205858
Herkunft:	Zweitveröffentlichung DeepGreen
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.
Alternatives oder übersetztes Abstract:	Alternatives Abstract Sprache Using a fragment-based screening strategy by NMR, we identified 311 small molecule binders of 25 SARS-CoV-2 proteins, thus expanding the previously unexplored chemical and target space. Further, using experimental and bioinformatic analysis we identify potential binding sites. This comprehensive data would greatly assist medicinal chemistry efforts even beyond COVID-19. Englisch
Freie Schlagworte:	COVID19-NMR, Drug Discovery, Fragment Screening, NMR Spectroscopy, Protein, SARS-CoV-2
ID-Nummer:	e202205858
Status:	Verlagsversion
URN:	urn:nbn:de:tuda-tuprints-229100
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
Fachbereich(e)/-gebiet(e):	10 Fachbereich Biologie 10 Fachbereich Biologie > RNA Biochemie
Hinterlegungsdatum:	22 Jan 2024 13:48
Letzte Änderung:	23 Jan 2024 08:03
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Verfügbare Versionen dieses Eintrags

• Comprehensive Fragment Screening of the SARS‐CoV‐2 Proteome Explores Novel Chemical Space for Drug Development. (deposited 22 Jan 2024 13:48) [Gegenwärtig angezeigt]
  • Comprehensive fragment screening of the SARS‐CoV‐2 proteome explores novel chemical space for drug development. (deposited 23 Jan 2024 08:04)

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