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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

: Bertoglio, Federico; Fühner, Viola; Ruschig, Maximilian; Heine, Philip Alexander; Abassi, Leila; Klünemann, Thomas; Rand, Ulfert; Meier, Doris; Langreder, Nora; Steinke, Stephan; Ballmann, Rico; Schneider, Kai-Thomas; Roth, Kristian Daniel Ralph; Kuhn, Philipp; Riese, Peggy; Schäckermann, Dorina; Korn, Janin; Koch, Allan; Chaudhry, M. Zeeshan; Eschke, Kathrin; Kim, Yeonsu; Zock-Emmenthal, Susanne; Becker, Marlies; Scholz, Margitta; Schmidt Garcia Moreira, Gustavo Marçal; Wenzel, Esther Veronika; Russo, Giulio; Garritsen, Hendrikus S.P.; Casu, Sebastian; Gerstner, Andreas; Roth, Günter; Adler, Julia; Trimpert, Jakob; Hermann, Andreas; Schirrmann, Thomas; Dübel, Stefan; Frenzel, André; Heuvel, Joop van den; Čičin-Šain, Luka; Schubert, Maren; Hust, Michael

Volltext ()

Cell reports 36 (2021), Nr.4, Art. 109433, 23 S.
ISSN: 2211-1247
Zeitschriftenaufsatz, Elektronische Publikation
Fraunhofer IST ()
SARS-CoV-2; coronavirus; RBD; SARS-CoV-2 variants

The novel betacoronavirus severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) causes a form of severe pneumonia disease called coronavirus disease 2019 (COVID-19). To develop human neutralizing anti-SARS-CoV-2 antibodies, antibody gene libraries from convalescent COVID-19 patients were constructed and recombinant antibody fragments (scFv) against the receptor-binding domain (RBD) of the spike protein were selected by phage display. The antibody STE90-C11 shows a subnanometer IC50 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.