Converting non-neutralizing SARS-CoV-2 antibodies into broad-spectrum inhibitors
© 2022. The Author(s)..
Omicron and its subvariants have rendered most authorized monoclonal antibody-based treatments for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ineffective, highlighting the need for biologics capable of overcoming SARS-CoV-2 evolution. These mostly ineffective antibodies target variable epitopes. Here we describe broad-spectrum SARS-CoV-2 inhibitors developed by tethering the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), to known non-neutralizing antibodies that target highly conserved epitopes in the viral spike protein. These inhibitors, called receptor-blocking conserved non-neutralizing antibodies (ReconnAbs), potently neutralize all SARS-CoV-2 variants of concern (VOCs), including Omicron. Neutralization potency is lost when the linker joining the binding and inhibitory ReconnAb components is severed. In addition, a bi-functional ReconnAb, made by linking ACE2 to a bi-specific antibody targeting two non-overlapping conserved epitopes, defined here, shows sub-nanomolar neutralizing activity against all VOCs, including Omicron and BA.2. Given their conserved targets and modular nature, ReconnAbs have the potential to act as broad-spectrum therapeutics against SARS-CoV-2 and other emerging pandemic diseases.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
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| Enthalten in: |
Nature chemical biology - 18(2022), 11 vom: 08. Nov., Seite 1270-1276 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Weidenbacher, Payton A-B [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 27.10.2022 Date Revised 27.05.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41589-022-01140-1 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Converting non-neutralizing SARS-CoV-2 antibodies into broad-spectrum inhibitors |
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| 520 | |a © 2022. The Author(s). | ||
| 520 | |a Omicron and its subvariants have rendered most authorized monoclonal antibody-based treatments for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ineffective, highlighting the need for biologics capable of overcoming SARS-CoV-2 evolution. These mostly ineffective antibodies target variable epitopes. Here we describe broad-spectrum SARS-CoV-2 inhibitors developed by tethering the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), to known non-neutralizing antibodies that target highly conserved epitopes in the viral spike protein. These inhibitors, called receptor-blocking conserved non-neutralizing antibodies (ReconnAbs), potently neutralize all SARS-CoV-2 variants of concern (VOCs), including Omicron. Neutralization potency is lost when the linker joining the binding and inhibitory ReconnAb components is severed. In addition, a bi-functional ReconnAb, made by linking ACE2 to a bi-specific antibody targeting two non-overlapping conserved epitopes, defined here, shows sub-nanomolar neutralizing activity against all VOCs, including Omicron and BA.2. Given their conserved targets and modular nature, ReconnAbs have the potential to act as broad-spectrum therapeutics against SARS-CoV-2 and other emerging pandemic diseases | ||
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| 700 | 1 | |a de Los Rios Kobara, Izumi |e verfasserin |4 aut | |
| 700 | 1 | |a Bell, Benjamin N |e verfasserin |4 aut | |
| 700 | 1 | |a Morris, Mary Kate |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Ya-Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Hanson, Carl |e verfasserin |4 aut | |
| 700 | 1 | |a Pak, John E |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Peter S |e verfasserin |4 aut | |
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