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A novel antibody against the furin cleavage site of SARS-CoV-2 spike protein: Effects on proteolytic cleavage and ACE2 binding
SARS-CoV-2 harbors a unique S1/S2 furin cleavage site within its spike protein, which can be cleaved by furin and other proprotein convertases. Proteolytic activation of SARS-CoV-2 spike protein at the S1/S2 boundary facilitates interaction with host ACE2 receptor for cell entry. To address this, hi...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
European Federation of Immunological Societies. Published by Elsevier B.V.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8739817/ https://www.ncbi.nlm.nih.gov/pubmed/35007661 http://dx.doi.org/10.1016/j.imlet.2022.01.002 |
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author | Spelios, Michael G. Capanelli, Jeanne M. Li, Adam W. |
author_facet | Spelios, Michael G. Capanelli, Jeanne M. Li, Adam W. |
author_sort | Spelios, Michael G. |
collection | PubMed |
description | SARS-CoV-2 harbors a unique S1/S2 furin cleavage site within its spike protein, which can be cleaved by furin and other proprotein convertases. Proteolytic activation of SARS-CoV-2 spike protein at the S1/S2 boundary facilitates interaction with host ACE2 receptor for cell entry. To address this, high titer antibody was generated against the SARS-CoV-2-specific furin motif. Using a series of innovative ELISA-based assays, this furin site blocking antibody displayed high sensitivity and specificity for the S1/S2 furin cleavage site, including with a P681R mutation, and demonstrated effective blockage of both enzyme-mediated cleavage and spike-ACE2 interaction. The results suggest that immunological blocking of the furin cleavage site may afford a suitable approach to stem proteolytic activation of SARS-CoV-2 spike protein and curtail viral infectivity. |
format | Online Article Text |
id | pubmed-8739817 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | European Federation of Immunological Societies. Published by Elsevier B.V. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87398172022-01-07 A novel antibody against the furin cleavage site of SARS-CoV-2 spike protein: Effects on proteolytic cleavage and ACE2 binding Spelios, Michael G. Capanelli, Jeanne M. Li, Adam W. Immunol Lett Article SARS-CoV-2 harbors a unique S1/S2 furin cleavage site within its spike protein, which can be cleaved by furin and other proprotein convertases. Proteolytic activation of SARS-CoV-2 spike protein at the S1/S2 boundary facilitates interaction with host ACE2 receptor for cell entry. To address this, high titer antibody was generated against the SARS-CoV-2-specific furin motif. Using a series of innovative ELISA-based assays, this furin site blocking antibody displayed high sensitivity and specificity for the S1/S2 furin cleavage site, including with a P681R mutation, and demonstrated effective blockage of both enzyme-mediated cleavage and spike-ACE2 interaction. The results suggest that immunological blocking of the furin cleavage site may afford a suitable approach to stem proteolytic activation of SARS-CoV-2 spike protein and curtail viral infectivity. European Federation of Immunological Societies. Published by Elsevier B.V. 2022-02 2022-01-07 /pmc/articles/PMC8739817/ /pubmed/35007661 http://dx.doi.org/10.1016/j.imlet.2022.01.002 Text en © 2022 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved. 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 Spelios, Michael G. Capanelli, Jeanne M. Li, Adam W. A novel antibody against the furin cleavage site of SARS-CoV-2 spike protein: Effects on proteolytic cleavage and ACE2 binding |
title | A novel antibody against the furin cleavage site of SARS-CoV-2 spike protein: Effects on proteolytic cleavage and ACE2 binding |
title_full | A novel antibody against the furin cleavage site of SARS-CoV-2 spike protein: Effects on proteolytic cleavage and ACE2 binding |
title_fullStr | A novel antibody against the furin cleavage site of SARS-CoV-2 spike protein: Effects on proteolytic cleavage and ACE2 binding |
title_full_unstemmed | A novel antibody against the furin cleavage site of SARS-CoV-2 spike protein: Effects on proteolytic cleavage and ACE2 binding |
title_short | A novel antibody against the furin cleavage site of SARS-CoV-2 spike protein: Effects on proteolytic cleavage and ACE2 binding |
title_sort | novel antibody against the furin cleavage site of sars-cov-2 spike protein: effects on proteolytic cleavage and ace2 binding |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8739817/ https://www.ncbi.nlm.nih.gov/pubmed/35007661 http://dx.doi.org/10.1016/j.imlet.2022.01.002 |
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