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PDBsum entry 7dcc
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Viral protein
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PDB id
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7dcc
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Contents |
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221 a.a.
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1061 a.a.
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213 a.a.
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References listed in PDB file
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Key reference
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Title
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Development and structural basis of a two-Mab cocktail for treating sars-Cov-2 infections.
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Authors
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C.Zhang,
Y.Wang,
Y.Zhu,
C.Liu,
C.Gu,
S.Xu,
Y.Wang,
Y.Zhou,
Y.Wang,
W.Han,
X.Hong,
Y.Yang,
X.Zhang,
T.Wang,
C.Xu,
Q.Hong,
S.Wang,
Q.Zhao,
W.Qiao,
J.Zang,
L.Kong,
F.Wang,
H.Wang,
D.Qu,
D.Lavillette,
H.Tang,
Q.Deng,
Y.Xie,
Y.Cong,
Z.Huang.
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Ref.
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Nat Commun, 2021,
12,
264.
[DOI no: ]
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PubMed id
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Abstract
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The ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutralizing antibodies
against SARS-CoV-2 are an option for drug development for treating COVID-19.
Here, we report the identification and characterization of two groups of mouse
neutralizing monoclonal antibodies (MAbs) targeting the receptor-binding domain
(RBD) on the SARS-CoV-2 spike (S) protein. MAbs 2H2 and 3C1, representing the
two antibody groups, respectively, bind distinct epitopes and are compatible in
formulating a noncompeting antibody cocktail. A humanized version of the 2H2/3C1
cocktail is found to potently neutralize authentic SARS-CoV-2 infection in vitro
with half inhibitory concentration (IC50) of 12 ng/mL and effectively treat
SARS-CoV-2-infected mice even when administered at as late as 24 h
post-infection. We determine an ensemble of cryo-EM structures of 2H2 or 3C1 Fab
in complex with the S trimer up to 3.8 Å resolution, revealing the
conformational space of the antigen-antibody complexes and MAb-triggered
stepwise allosteric rearrangements of the S trimer, delineating a previously
uncharacterized dynamic process of coordinated binding of neutralizing
antibodies to the trimeric S protein. Our findings provide important information
for the development of MAb-based drugs for preventing and treating SARS-CoV-2
infections.
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