1. Comprehensive Fragment Screening of the SARS-CoV-2 Proteome Explores Novel Chemical Space for Drug Development.
- Author
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Berg H, Wirtz Martin MA, Altincekic N, Alshamleh I, Kaur Bains J, Blechar J, Ceylan B, de Jesus V, Dhamotharan K, Fuks C, Gande SL, Hargittay B, Hohmann KF, Hutchison MT, Marianne Korn S, Krishnathas R, Kutz F, Linhard V, Matzel T, Meiser N, Niesteruk A, Pyper DJ, Schulte L, Trucks S, Azzaoui K, Blommers MJJ, Gadiya Y, Karki R, Zaliani A, Gribbon P, da Silva Almeida M, Dinis Anobom C, Bula AL, Bütikofer M, Putinhon Caruso Í, Caterina Felli I, Da Poian AT, Cardoso de Amorim G, Fourkiotis NK, Gallo A, Ghosh D, Gomes-Neto F, Gorbatyuk O, Hao B, Kurauskas V, Lecoq L, Li Y, Cunha Mebus-Antunes N, Mompeán M, Cristtina Neves-Martins T, Ninot-Pedrosa M, Pinheiro AS, Pontoriero L, Pustovalova Y, Riek R, Robertson AJ, Jose Abi Saad M, Treviño MÁ, Tsika AC, Almeida FCL, Bax A, Henzler-Wildman K, Hoch JC, Jaudzems K, Laurents DV, Orts J, Pierattelli R, Spyroulias GA, Duchardt-Ferner E, Ferner J, Fürtig B, Hengesbach M, Löhr F, Qureshi N, Richter C, Saxena K, Schlundt A, Sreeramulu S, Wacker A, Weigand JE, Wirmer-Bartoschek J, Wöhnert J, and Schwalbe H more...
- Subjects
- Humans, Proteome, Ligands, Drug Design, SARS-CoV-2, COVID-19 Drug Treatment
- 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., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.) more...
- Published
- 2022
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