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PDBsum entry 7cwl
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Viral protein
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PDB id
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7cwl
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Contents |
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1073 a.a.
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120 a.a.
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108 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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Rational development of a human antibody cocktail that deploys multiple functions to confer pan-Sars-Covs protection.
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Authors
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H.Yao,
Y.Sun,
Y.Q.Deng,
N.Wang,
Y.Tan,
N.N.Zhang,
X.F.Li,
C.Kong,
Y.P.Xu,
Q.Chen,
T.S.Cao,
H.Zhao,
X.Yan,
L.Cao,
Z.Lv,
D.Zhu,
R.Feng,
N.Wu,
W.Zhang,
Y.Hu,
K.Chen,
R.R.Zhang,
Q.Lv,
S.Sun,
Y.Zhou,
R.Yan,
G.Yang,
X.Sun,
C.Liu,
X.Lu,
L.Cheng,
H.Qiu,
X.Y.Huang,
T.Weng,
D.Shi,
W.Jiang,
J.Shao,
L.Wang,
J.Zhang,
T.Jiang,
G.Lang,
C.F.Qin,
L.Li,
X.Wang.
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Ref.
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Cell Res, 2021,
31,
25-36.
[DOI no: ]
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PubMed id
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DOI number
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Abstract
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Structural principles underlying the composition and synergistic mechanisms of
protective monoclonal antibody cocktails are poorly defined. Here, we exploited
antibody cooperativity to develop a therapeutic antibody cocktail against
SARS-CoV-2. On the basis of our previously identified humanized
cross-neutralizing antibody H014, we systematically analyzed a fully human naive
antibody library and rationally identified a potent neutralizing antibody
partner, P17, which confers effective protection in animal model. Cryo-EM
studies dissected the nature of the P17 epitope, which is SARS-CoV-2 specific
and distinctly different from that of H014. High-resolution structure of the
SARS-CoV-2 spike in complex with H014 and P17, together with functional
investigations revealed that in a two-antibody cocktail, synergistic
neutralization was achieved by S1 shielding and conformational locking, thereby
blocking receptor attachment and viral membrane fusion, conferring high potency
as well as robustness against viral mutation escape. Furthermore, cluster
analysis identified a hypothetical 3rd antibody partner for further reinforcing
the cocktail as pan-SARS-CoVs therapeutics.
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