In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 8 ( 2022-8-10), p. e0272364-
Abstract:
Neutralizing antibodies targeting the SARS-CoV-2 spike protein have shown a great preventative/therapeutic potential. Here, we report a rapid and efficient strategy for the development and design of SARS-CoV-2 neutralizing humanized nanobody constructs with sub-nanomolar affinities and nanomolar potencies. CryoEM-based structural analysis of the nanobodies in complex with spike revealed two distinct binding modes. The most potent nanobody, RBD-1-2G(NCATS-BL8125), tolerates the N501Y RBD mutation and remains capable of neutralizing the B.1.1.7 (Alpha) variant. Molecular dynamics simulations provide a structural basis for understanding the neutralization process of nanobodies exclusively focused on the spike-ACE2 interface with and without the N501Y mutation on RBD. A primary human airway air-lung interface (ALI) ex vivo model showed that RBD-1-2G-Fc antibody treatment was effective at reducing viral burden following WA1 and B.1.1.7 SARS-CoV-2 infections. Therefore, this presented strategy will serve as a tool to mitigate the threat of emerging SARS-CoV-2 variants.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0272364
DOI:
10.1371/journal.pone.0272364.g001
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10.1371/journal.pone.0272364.g002
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10.1371/journal.pone.0272364.g003
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10.1371/journal.pone.0272364.g005
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10.1371/journal.pone.0272364.s001
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10.1371/journal.pone.0272364.s002
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10.1371/journal.pone.0272364.s003
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10.1371/journal.pone.0272364.s016
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10.1371/journal.pone.0272364.s017
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10.1371/journal.pone.0272364.s019
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10.1371/journal.pone.0272364.s020
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10.1371/journal.pone.0272364.s021
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10.1371/journal.pone.0272364.s022
DOI:
10.1371/journal.pone.0272364.s023
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2267670-3
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