Comprehensive Fragment Screening of the SARS-CoV-2 Proteome Explores Novel Chemical Space for Drug Development
- Author(s)
- 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 Meiser, Anna 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
- 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.
- Organisation(s)
- Department of Pharmaceutical Sciences
- External organisation(s)
- Johann Wolfgang Goethe-Universität Frankfurt am Main, Saverna Therapeut, Universidade Federal do Rio de Janeiro, Latvian Institute of Organic Synthesis, Eidgenössische Technische Hochschule Zürich, Universidade Estadual Paulista „Júlio de Mesquita Filho“, University of Florence, University of Patras, University of Turin, Oswaldo Cruz Foundation, University of Wisconsin, Madison, Centre National De La Recherche Scientifique (CNRS), Spanish National Research Council (CSIC), Technische Universität Darmstadt, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Schnackenburgallee 114, 22525, Hamburg, Germany., University of Connecticut, National Institute of Diabetes and Digestive and Kidney Diseases, Instituto de Física Corpuscular (IFIC)
- Journal
- Angewandte Chemie International Edition
- Volume
- 61
- No. of pages
- 12
- ISSN
- 1433-7851
- DOI
- https://doi.org/10.1002/anie.202205858
- Publication date
- 11-2022
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 106002 Biochemistry, 106006 Biophysics
- Keywords
- ASJC Scopus subject areas
- General Biochemistry,Genetics and Molecular Biology, Biophysics
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/f60e2244-5b39-44ca-8497-5ca228028839