A potent neutralizing nanobody targeting a unique epitope on the receptor-binding domain of SARS-CoV-2 spike protein
Copyright © 2023 Elsevier Inc. All rights reserved..
SARS-CoV-2 and its variants continue to threaten public health. Nanobodies that block the attachment of the RBD to host cell angiotensin-converting enzyme 2 (ACE2) represent promising drug candidates. In this study, we reported the identification and structural biological characterization of a nanobody from a RBD-immunized alpaca. The nanobody, termed as 2S-1-19, shows outstanding neutralizing activity against both pseudotyped and authentic SARS-CoV-2 viruses. The crystal structure of 2S-1-19 bound to SARS-CoV-2 RBD reveals an epitope that overlaps with the binding site for ACE2. We also showed that 2S-1-19 reserves promising, though compromised, neutralizing activity against the Delta variant and that the trivalent form of 2S-1-19 remarkably increases its neutralizing capacity. Despite this, neither the monomeric or trimeric 2S-1-19 could neutralize the Omicron BA.1.1 variant, possibility due to the E484A and Q493K mutations found within this virus variant. These data provide insights into immune evasion caused by SARS-CoV-2 variants.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 2023 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:589 |
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| Enthalten in: |
Virology - 589(2023) vom: 15. Jan., Seite 109925 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Yuting [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.12.2023 Date Revised 16.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.virol.2023.109925 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 2 | |a A potent neutralizing nanobody targeting a unique epitope on the receptor-binding domain of SARS-CoV-2 spike protein |
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| 520 | |a Copyright © 2023 Elsevier Inc. All rights reserved. | ||
| 520 | |a SARS-CoV-2 and its variants continue to threaten public health. Nanobodies that block the attachment of the RBD to host cell angiotensin-converting enzyme 2 (ACE2) represent promising drug candidates. In this study, we reported the identification and structural biological characterization of a nanobody from a RBD-immunized alpaca. The nanobody, termed as 2S-1-19, shows outstanding neutralizing activity against both pseudotyped and authentic SARS-CoV-2 viruses. The crystal structure of 2S-1-19 bound to SARS-CoV-2 RBD reveals an epitope that overlaps with the binding site for ACE2. We also showed that 2S-1-19 reserves promising, though compromised, neutralizing activity against the Delta variant and that the trivalent form of 2S-1-19 remarkably increases its neutralizing capacity. Despite this, neither the monomeric or trimeric 2S-1-19 could neutralize the Omicron BA.1.1 variant, possibility due to the E484A and Q493K mutations found within this virus variant. These data provide insights into immune evasion caused by SARS-CoV-2 variants | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Wang, Dan |e verfasserin |4 aut | |
| 700 | 1 | |a Xiang, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Xiaohui |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yuting |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Lijie |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zhaoyong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yanqun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jincun |e verfasserin |4 aut | |
| 700 | 1 | |a McCormick, Peter J |e verfasserin |4 aut | |
| 700 | 1 | |a Fu, Jinheng |e verfasserin |4 aut | |
| 700 | 1 | |a Fu, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Haihai |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jian |e verfasserin |4 aut | |
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