Development of humanized tri-specific nanobodies with potent neutralization for SARS-CoV-2
SARS-CoV-2 is a newly emergent coronavirus, which has adversely impacted human health and has led to the COVID-19 pandemic. There is an unmet need to develop therapies against SARS-CoV-2 due to its severity and lack of treatment options. A promising approach to combat COVID-19 is through the neutralization of SARS-CoV-2 by therapeutic antibodies. Previously, we described a strategy to rapidly identify and generate llama nanobodies (VHH) from naïve and synthetic humanized VHH phage libraries that specifically bind the S1 SARS-CoV-2 spike protein, and block the interaction with the human ACE2 receptor. In this study we used computer-aided design to construct multi-specific VHH antibodies fused to human IgG1 Fc domains based on the epitope predictions for leading VHHs. The resulting tri-specific VHH-Fc antibodies show more potent S1 binding, S1/ACE2 blocking, and SARS-CoV-2 pseudovirus neutralization than the bi-specific VHH-Fcs or combination of individual monoclonal VHH-Fcs. Furthermore, protein stability analysis of the VHH-Fcs shows favorable developability features, which enable them to be quickly and successfully developed into therapeutics against COVID-19.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Scientific reports - 10(2020), 1 vom: 20. Okt., Seite 17806 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dong, Jianbo [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 04.11.2020 Date Revised 30.03.2024 published: Electronic ErratumIn: Sci Rep. 2021 Feb 17;11(1):4371. - PMID 33597581 Citation Status MEDLINE |
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| doi: |
10.1038/s41598-020-74761-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM316517216 |
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| 500 | |a ErratumIn: Sci Rep. 2021 Feb 17;11(1):4371. - PMID 33597581 | ||
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| 520 | |a SARS-CoV-2 is a newly emergent coronavirus, which has adversely impacted human health and has led to the COVID-19 pandemic. There is an unmet need to develop therapies against SARS-CoV-2 due to its severity and lack of treatment options. A promising approach to combat COVID-19 is through the neutralization of SARS-CoV-2 by therapeutic antibodies. Previously, we described a strategy to rapidly identify and generate llama nanobodies (VHH) from naïve and synthetic humanized VHH phage libraries that specifically bind the S1 SARS-CoV-2 spike protein, and block the interaction with the human ACE2 receptor. In this study we used computer-aided design to construct multi-specific VHH antibodies fused to human IgG1 Fc domains based on the epitope predictions for leading VHHs. The resulting tri-specific VHH-Fc antibodies show more potent S1 binding, S1/ACE2 blocking, and SARS-CoV-2 pseudovirus neutralization than the bi-specific VHH-Fcs or combination of individual monoclonal VHH-Fcs. Furthermore, protein stability analysis of the VHH-Fcs shows favorable developability features, which enable them to be quickly and successfully developed into therapeutics against COVID-19 | ||
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| 700 | 1 | |a Gallolu Kankanamalage, Sachith |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Zhejun |e verfasserin |4 aut | |
| 700 | 1 | |a Wright, Meredith |e verfasserin |4 aut | |
| 700 | 1 | |a Parthasarathy, Pannaga |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yue |e verfasserin |4 aut | |
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