title: Comprehensive Fragment Screening of the SARS‐CoV‐2 Proteome Explores Novel Chemical Space for Drug Development
Creators: name: Berg, Hannes
name: Wirtz Martin, Maria A.
name: Altincekic, Nadide
name: Alshamleh, Islam
name: Kaur Bains, Jasleen
name: Blechar, Julius
name: Ceylan, Betül
name: Jesus, Vanessa de
name: Dhamotharan, Karthikeyan
name: Fuks, Christin
name: Gande, Santosh L.
name: Hargittay, Bruno
name: Hohmann, Katharina F.
name: Hutchison, Marie T.
name: Korn, Sophie Marianne
name: Krishnathas, Robin
name: Kutz, Felicitas
name: Linhard, Verena
name: Matzel, Tobias
name: Meiser, Nathalie
name: Niesteruk, Anna
name: Pyper, Dennis J.
name: Schulte, Linda
name: Trucks, Sven
name: Azzaoui, Kamal
name: Blommers, Marcel J. J.
name: Gadiya, Yojana
name: Karki, Reagon
name: Zaliani, Andrea
name: Gribbon, Philip
name: Silva Almeida, Marcius da
name: Dinis Anobom, Cristiane
name: Bula, Anna L.
name: Bütikofer, Matthias
name: Putinhon Caruso, Ícaro
name: Caterina Felli, Isabella
name: Da Poian, Andrea T.
name: Cardoso de Amorim, Gisele
name: Fourkiotis, Nikolaos K.
name: Gallo, Angelo
name: Ghosh, Dhiman
name: Gomes‐Neto, Francisco
name: Gorbatyuk, Oksana
name: Hao, Bing
name: Kurauskas, Vilius
name: Lecoq, Lauriane
name: Li, Yunfeng
name: Cunha Mebus‐Antunes, Nathane
name: Mompeán, Miguel
name: Cristtina Neves‐Martins, Thais
name: Ninot‐Pedrosa, Martí
name: Pinheiro, Anderson S.
name: Pontoriero, Letizia
name: Pustovalova, Yulia
name: Riek, Roland
name: Robertson, Angus J.
name: Jose Abi Saad, Marie
name: Treviño, Miguel Á.
name: Tsika, Aikaterini C.
name: Almeida, Fabio C. L.
name: Bax, Ad
name: Henzler‐Wildman, Katherine
name: Hoch, Jeffrey C.
name: Jaudzems, Kristaps
name: Laurents, Douglas V.
name: Orts, Julien
name: Pierattelli, Roberta
name: Spyroulias, Georgios A.
name: Duchardt‐Ferner, Elke
name: Ferner, Jan
name: Fürtig, Boris
name: Hengesbach, Martin
name: Löhr, Frank
name: Qureshi, Nusrat
name: Richter, Christian
name: Saxena, Krishna
name: Schlundt, Andreas
name: Sreeramulu, Sridhar
name: Wacker, Anna
name: Weigand, Julia E.
name: Wirmer‐Bartoschek, Julia
name: Wöhnert, Jens
name: Schwalbe, Harald
Publisher: name: Wiley-VCH
Year: 2024

description: 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.