Comprehensive Fragment Screening of the SARS-CoV-2 Proteome Explores Novel Chemical Space for Drug Development

Hannes Berg, Maria A. Wirtz Martin, Nadide Altincekic, Islam Alshamleh, Jasleen Kaur Bains, Julius Blechar, Betul Ceylan, Vanessa de Jesus, Karthikeyan Dhamotharan, Christin Fuks, Santosh L. Gande, Bruno Hargittay, Katharina F. Hohmann, Marie T. Hutchison, Sophie Marianne Korn, Robin Krishnathas, Felicitas Kutz, Verena Linhard, Tobias Matzel, Nathalie MeiserAnna Niesteruk, Dennis J. Pyper, Linda Schulte, Sven Trucks, Kamal Azzaoui, Marcel J. J. Blommers, Yojana Gadiya, Reagon Karki, Andrea Zaliani, Philip Gribbon, Marcius da Silva Almeida, Cristiane Dinis Anobom, Anna L. Bula, Matthias Butikofer, Icaro Putinhon Caruso, Isabella Caterina Felli, Andrea T. Da Poian, Gisele Cardoso de Amorim, Nikolaos K. Fourkiotis, Angelo Gallo, Dhiman Ghosh, Francisco Gomes-Neto, Oksana Gorbatyuk, Bing Hao, Vilius Kurauskas, Lauriane Lecoq, Yunfeng Li, Nathane Cunha Mebus-Antunes, Miguel Mompean, Thais Cristtina Neves-Martins, Marti Ninot-Pedrosa, Anderson S. Pinheiro, Letizia Pontoriero, Yulia Pustovalova, Roland Riek, Angus J. Robertson, Marie Jose Abi Saad, Miguel A. Trevino, Aikaterini C. Tsika, Fabio C. L. Almeida, Ad Bax, Katherine Henzler-Wildman, Jeffrey C. Hoch, Kristaps Jaudzems, Douglas Laurents, Julien Orts, Roberta Pierattelli, Georgios A. Spyroulias, Elke Duchardt-Ferner, Jan Ferner, Boris Fürtig, Martin Hengesbach, Frank Lohr, Nusrat Qureshi, Christian Richter, Krishna Saxena, Andreas Schlundt, Sridhar Sreeramulu, Anna Wacker, Julia E. Weigand, Julia Wirmer-Bartoschek, Jens Wohnert, Harald Schwalbe

Veröffentlichungen: Beitrag in FachzeitschriftArtikelPeer Reviewed

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.
OriginalspracheEnglisch
Aufsatznummere202205858
Seitenumfang12
FachzeitschriftAngewandte Chemie International Edition
Jahrgang61
Ausgabenummer46
DOIs
PublikationsstatusVeröffentlicht - 14 Nov. 2022

ÖFOS 2012

  • 106002 Biochemie
  • 106006 Biophysik

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