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Human monoclonal antibodies to SARS-coronavirus inhibit infection by different mechanisms

SARS-CoV causes an acute infection making targeted passive immunotherapy an attractive treatment strategy. We previously generated human mAbs specific to the S1 region of SARS-CoV S protein. These mAbs bind epitopes within the receptor binding domain (RBD) or upstream of the RBD. We show that mAbs r...

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Detalles Bibliográficos
Autores principales: Coughlin, Melissa M., Babcook, John, Prabhakar, Bellur S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Inc. 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111986/
https://www.ncbi.nlm.nih.gov/pubmed/19748648
http://dx.doi.org/10.1016/j.virol.2009.07.028
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author Coughlin, Melissa M.
Babcook, John
Prabhakar, Bellur S.
author_facet Coughlin, Melissa M.
Babcook, John
Prabhakar, Bellur S.
author_sort Coughlin, Melissa M.
collection PubMed
description SARS-CoV causes an acute infection making targeted passive immunotherapy an attractive treatment strategy. We previously generated human mAbs specific to the S1 region of SARS-CoV S protein. These mAbs bind epitopes within the receptor binding domain (RBD) or upstream of the RBD. We show that mAbs recognizing epitopes within the RBD inhibit infection by preventing viral attachment to the cellular receptor. One mAb binds upstream of the RBD and prevents viral entry by inhibiting a post-binding event. Evaluation of several mAbs demonstrated varying ability of the mAbs to select escape mutants when used individually. However, a mixture of antibodies could effectively neutralize a range of mutant viruses. These data strongly suggest that a mixture containing antibodies recognizing distinct regions and targeting more than one step in viral entry is likely to be more effective in neutralizing the virus and suppressing the generation of escape mutants, and thus potentially constitute a highly effective passive immunotherapy.
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spelling pubmed-71119862020-04-02 Human monoclonal antibodies to SARS-coronavirus inhibit infection by different mechanisms Coughlin, Melissa M. Babcook, John Prabhakar, Bellur S. Virology Article SARS-CoV causes an acute infection making targeted passive immunotherapy an attractive treatment strategy. We previously generated human mAbs specific to the S1 region of SARS-CoV S protein. These mAbs bind epitopes within the receptor binding domain (RBD) or upstream of the RBD. We show that mAbs recognizing epitopes within the RBD inhibit infection by preventing viral attachment to the cellular receptor. One mAb binds upstream of the RBD and prevents viral entry by inhibiting a post-binding event. Evaluation of several mAbs demonstrated varying ability of the mAbs to select escape mutants when used individually. However, a mixture of antibodies could effectively neutralize a range of mutant viruses. These data strongly suggest that a mixture containing antibodies recognizing distinct regions and targeting more than one step in viral entry is likely to be more effective in neutralizing the virus and suppressing the generation of escape mutants, and thus potentially constitute a highly effective passive immunotherapy. Elsevier Inc. 2009-11-10 2009-09-12 /pmc/articles/PMC7111986/ /pubmed/19748648 http://dx.doi.org/10.1016/j.virol.2009.07.028 Text en Copyright © 2009 Elsevier Inc. 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
Coughlin, Melissa M.
Babcook, John
Prabhakar, Bellur S.
Human monoclonal antibodies to SARS-coronavirus inhibit infection by different mechanisms
title Human monoclonal antibodies to SARS-coronavirus inhibit infection by different mechanisms
title_full Human monoclonal antibodies to SARS-coronavirus inhibit infection by different mechanisms
title_fullStr Human monoclonal antibodies to SARS-coronavirus inhibit infection by different mechanisms
title_full_unstemmed Human monoclonal antibodies to SARS-coronavirus inhibit infection by different mechanisms
title_short Human monoclonal antibodies to SARS-coronavirus inhibit infection by different mechanisms
title_sort human monoclonal antibodies to sars-coronavirus inhibit infection by different mechanisms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111986/
https://www.ncbi.nlm.nih.gov/pubmed/19748648
http://dx.doi.org/10.1016/j.virol.2009.07.028
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