A SARS-CoV-2 neutralizing antibody selected from COVID-19 patients binds to the ACE2-RBD interface and is tolerant to most known RBD mutations
Federico Bertoglio, Viola Fühner, Maximilian Ruschig, Philip Alexander Heine, Leila Abassi, Thomas Klünemann, Ulfert Rand, Doris Meier, Nora Langreder, Stephan Steinke, Rico Ballmann, Kai-Thomas Schneider, Kristian Daniel Ralph Roth, Philipp Kühn, Peggy Riese, Dorina Schäckermann, Janin Korn, Allan Koch, M. Zeeshan Chaudhry, Kathrin Eschke, Yeonsu Kim, Susanne Zock‐Emmenthal, Marlies Becker, M Scholz, Gustavo Marçal Schmidt Garcia Moreira, Esther Veronika Wenzel, Giulio Russo, Hendrikus S.P. Garritsen, Sebastian Casu, Andreas O. H. Gerstner, Günter Roth, Julia M. Adler, Jakob Trimpert, Andreas Hermann, Thomas Schirrmann, Stefan Dübel, André Frenzel, Joop van den Heuvel, Luka Čičin‐Šain, Maren Schubert, Michael Hust
Abstract
in a plaque-based live SARS-CoV-2 neutralization assay. The in vivo efficacy of the antibody is demonstrated in the Syrian hamster and in the human angiotensin-converting enzyme 2 (hACE2) mice model. The crystal structure of STE90-C11 Fab in complex with SARS-CoV-2-RBD is solved at 2.0 Å resolution showing that the antibody binds at the same region as ACE2 to RBD. The binding and inhibition of STE90-C11 is not blocked by many known emerging RBD mutations. STE90-C11-derived human IgG1 with FcγR-silenced Fc (COR-101) is undergoing Phase Ib/II clinical trials for the treatment of moderate to severe COVID-19.