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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
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 cons...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
The Author(s).
2021
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260561/ https://www.ncbi.nlm.nih.gov/pubmed/34273271 http://dx.doi.org/10.1016/j.celrep.2021.109433 |
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| author | 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 Moreira, Gustavo Marçal Schmidt Garcia 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 Van den Heuvel, Joop Čičin-Šain, Luka Schubert, Maren Hust, Michael |
| author_facet | 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 Moreira, Gustavo Marçal Schmidt Garcia 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 Van den Heuvel, Joop Čičin-Šain, Luka Schubert, Maren Hust, Michael |
| author_sort | Bertoglio, Federico |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-8260561 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2021 |
| publisher | The Author(s). |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-82605612021-07-07 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 Moreira, Gustavo Marçal Schmidt Garcia 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 Van den Heuvel, Joop Čičin-Šain, Luka Schubert, Maren Hust, Michael Cell Rep Article 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. The Author(s). 2021-07-27 2021-07-07 /pmc/articles/PMC8260561/ /pubmed/34273271 http://dx.doi.org/10.1016/j.celrep.2021.109433 Text en © 2021 The Author(s) Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
| spellingShingle | Article 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 Moreira, Gustavo Marçal Schmidt Garcia 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 Van den Heuvel, Joop Čičin-Šain, Luka Schubert, Maren Hust, Michael 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 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | sars-cov-2 neutralizing antibody selected from covid-19 patients binds to the ace2-rbd interface and is tolerant to most known rbd mutations |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260561/ https://www.ncbi.nlm.nih.gov/pubmed/34273271 http://dx.doi.org/10.1016/j.celrep.2021.109433 |
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