1. A SARS-CoV-2 Neutralizing Antibody Selected from COVID-19 Patients by Phage Display is Binding to the ACE2-RBD Interface and is Tolerant to Known RBD Mutations
- Author
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Sebastian Casu, Maren Schubert, Peggy Riese, Esther Veronika Wenzel, Kristian Danial Ralph Roth, Margitta Scholz, André Frenzel, Michael Hust, Philipp Kuhn, Thomas Schirrmann, Hendrikus S.P. Garritsen, Janin Korn, Günter Roth, Federico Bertoglio, Andreas Gerstner, Giulio Russo, Andreas Hermann, Allan Koch, Ulfert Rand, Viola Fühner, Joop van den Heuvel, Marlies Becker, Gustavo Marçal Schmidt Garcia Moreira, Kai-Thomas Schneider, Philip Alexander Heine, Rico Ballmann, Maximilian Ruschig, Doris Meier, Nora Langreder, Dorina Schäckermann, Luka Cicin-Sain, Stefan Dübel, Susanne Zock-Emmenthal, Thomas Klünemann, and Stephan Steinke
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Phage display ,biology ,Protein subunit ,Virology ,Neutralization ,law.invention ,law ,Blocking antibody ,biology.protein ,Recombinant DNA ,media_common.cataloged_instance ,Antibody ,European union ,Neutralizing antibody ,media_common - Abstract
The novel betacoranavirus SARS-CoV-2 causes a form of severe pneumonia disease, termed COVID-19 (coronavirus disease 2019). Recombinant human antibodies are proven potent neutralizers of viruses and can block the interaction of viral surface proteins with their host receptors. To develop 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 S1 subunit of the viral spike (S) protein were selected by phage display. The selected antibodies were produced in the scFv-Fc format and 30 showed more than 80% inhibition of spike (S1-S2) binding to cells expressing ACE2, assessed by flow cytometry screening assay. The majority of these inhibiting antibodies are derived from the VH3-66 V-gene. The antibody STE90-C11 showed an IC50 of 0.56 nM in a plaque-based live SARS-CoV-2 neutralization assay. The crystal structure of STE90-C11 in complex with SARS-CoV-2-RBD was solved at 2.0 A resolution showing that the antibody binds at the same region as ACE2 to RBD. In contrast to other published anti-SARS-CoV-2 antibodies, the binding of STE90-C11 is not blocked by known RBD mutations, endowing our antibody with higher intrinsic resistance to those possible escape mutants. Funding: We kindly acknowledge the financial support of MWK Niedersachsen (14-76103-184CORONA-2/20) for antibody generation. We also acknowledge support of the European Union for the ATAC (“antibody therapy against corona”, Horizon 2020 number 101003650) consortium. Conflict of Interest: The authors declare a conflict of interest. F.B., D.M.,N.L., S.S., P.A.H., R.B., M.R., K.T.S.,K.D.R.R., S.Z.-E., M.B., V.F., S.T.,M.S. and M.H. are inventors on a patent application on blocking antibodies against SARS-CoV-2. A.H., A.F. and T.S. are officers of CORAT Therapeutics GmbH, a company founded by YUMAB GmbH for the clinical and regulatory development of STE90-C11 (COR-101). A.F., T.S., S.D. and M.H. are shareholders of YUMAB GmbH. Ethical Approval: Approval number, FV-2020-02. Approved by the TU Braunschweig Institute for Psychology.
- Published
- 2020
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