1. 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.
- Author
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Bertoglio F, Fühner V, Ruschig M, Heine PA, Abassi L, Klünemann T, Rand U, Meier D, Langreder N, Steinke S, Ballmann R, Schneider KT, Roth KDR, Kuhn P, Riese P, Schäckermann D, Korn J, Koch A, Chaudhry MZ, Eschke K, Kim Y, Zock-Emmenthal S, Becker M, Scholz M, Moreira GMSG, Wenzel EV, Russo G, Garritsen HSP, Casu S, Gerstner A, Roth G, Adler J, Trimpert J, Hermann A, Schirrmann T, Dübel S, Frenzel A, Van den Heuvel J, Čičin-Šain L, Schubert M, and Hust M
- Subjects
- COVID-19 virology, Humans, Mutation genetics, Peptidyl-Dipeptidase A metabolism, Protein Binding, Protein Domains genetics, Spike Glycoprotein, Coronavirus immunology, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, SARS-CoV-2 pathogenicity, Spike Glycoprotein, Coronavirus genetics
- Abstract
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 IC
50 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., Competing Interests: Declaration of interests F.B., D.M., N.L., S. Steinke, P.A.H., R.B., M.R., K.-T.S., K.D.R.R., S.Z.-E., M.B., V.F., S.D., M. Schubert, 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 (development name COR-101) (ClinicalTrials.gov ID: NCT04674566 for safety and efficacy of COR-101 in hospitalized patients with moderate to severe COVID-19). A.H. is a shareholder of CORAT Therapeutics GmbH. S.D. and M.H. are advisors to Corat Therapeutics GmbH. A.F., T.S., S.D., and M.H. are shareholders of YUMAB GmbH., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2021
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