In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 19, No. 1 ( 2023-1-27), p. e1011085-
Abstract:
Neutralizing antibodies (nAbs) are important assets to fight COVID-19, but most existing nAbs lose the activities against Omicron subvariants. Here, we report a human monoclonal antibody (Ab08) isolated from a convalescent patient infected with the prototype strain (Wuhan-Hu-1). Ab08 binds to the receptor-binding domain (RBD) with pico-molar affinity (230 pM ), effectively neutralizes SARS-CoV-2 and variants of concern (VOCs) including Alpha, Beta, Gamma, Mu, Omicron BA.1 and BA.2, and to a lesser extent for Delta and Omicron BA.4/BA.5 which bear the L452R mutation. Of medical importance, Ab08 shows therapeutic efficacy in SARS-CoV-2-infected hACE2 mice. X-ray crystallography of the Ab08-RBD complex reveals an antibody footprint largely in the β-strand core and away from the ACE2-binding motif. Negative staining electron-microscopy suggests a neutralizing mechanism through which Ab08 destructs the Spike trimer. Together, our work identifies a nAb with therapeutic potential for COVID-19.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1011085
DOI:
10.1371/journal.ppat.1011085.g001
DOI:
10.1371/journal.ppat.1011085.g002
DOI:
10.1371/journal.ppat.1011085.g003
DOI:
10.1371/journal.ppat.1011085.g004
DOI:
10.1371/journal.ppat.1011085.s001
DOI:
10.1371/journal.ppat.1011085.s002
DOI:
10.1371/journal.ppat.1011085.s003
DOI:
10.1371/journal.ppat.1011085.s004
DOI:
10.1371/journal.ppat.1011085.s005
DOI:
10.1371/journal.ppat.1011085.s006
DOI:
10.1371/journal.ppat.1011085.s007
DOI:
10.1371/journal.ppat.1011085.s008
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2205412-1
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