Comprehensive fragment screening of the SARS‐CoV‐2 proteome explores novel chemical space for drug development

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:

(Heft-)Nummer:

Kollation:

12 Seiten

DOI:

10.1002/anie.202205858

Zugehörige Links:

Kurzbeschreibung (Abstract):

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

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:

23 Jan 2024 08:04

Letzte Änderung:

23 Jan 2024 08:04

PPN:

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