Comprehensive Fragment Screening of the SARS‐CoV‐2 Proteome Explores Novel Chemical Space for Drug Development
Archive ouverte
Berg, Hannes | Wirtz Martin, Maria, A | Altincekic, Nadide | Alshamleh, Islam | Kaur Bains, Jasleen | Blechar, Julius | Ceylan, Betül | de Jesus, Vanessa | Dhamotharan, Karthikeyan | Fuks, Christin | Gande, Santosh, L | Hargittay, Bruno | Hohmann, Katharina, F | Hutchison, Marie, T | Marianne Korn, Sophie | 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 | da Silva Almeida, Marcius | 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
Edité par
CCSD ; Wiley-VCH Verlag -
International audience.
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.
