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PDBsum entry 7ch4
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Protein binding/immune system
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PDB id
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7ch4
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Contents |
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218 a.a.
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213 a.a.
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188 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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Structurally resolved sars-Cov-2 antibody shows high efficacy in severely infected hamsters and provides a potent cocktail pairing strategy.
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Authors
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S.Du,
Y.Cao,
Q.Zhu,
P.Yu,
F.Qi,
G.Wang,
X.Du,
L.Bao,
W.Deng,
H.Zhu,
J.Liu,
J.Nie,
Y.Zheng,
H.Liang,
R.Liu,
S.Gong,
H.Xu,
A.Yisimayi,
Q.Lv,
B.Wang,
R.He,
Y.Han,
W.Zhao,
Y.Bai,
Y.Qu,
X.Gao,
C.Ji,
Q.Wang,
N.Gao,
W.Huang,
Y.Wang,
X.S.Xie,
X.D.Su,
J.Xiao,
C.Qin.
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Ref.
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Cell, 2020,
183,
1013.
[DOI no: ]
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PubMed id
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Abstract
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Understanding how potent neutralizing antibodies (NAbs) inhibit SARS-CoV-2 is
critical for effective therapeutic development. We previously described
BD-368-2, a SARS-CoV-2 NAb with high potency; however, its neutralization
mechanism is largely unknown. Here, we report the 3.5-Å cryo-EM structure of
BD-368-2/trimeric-spike complex, revealing that BD-368-2 fully blocks ACE2
recognition by occupying all three receptor-binding domains (RBDs)
simultaneously, regardless of their "up" or "down"
conformations. Also, BD-368-2 treats infected adult hamsters at low dosages and
at various administering windows, in contrast to placebo hamsters that
manifested severe interstitial pneumonia. Moreover, BD-368-2's epitope
completely avoids the common binding site of VH3-53/VH3-66 recurrent NAbs,
evidenced by tripartite co-crystal structures with RBDs. Pairing BD-368-2 with a
potent recurrent NAb neutralizes SARS-CoV-2 pseudovirus at pM level and rescues
mutation-induced neutralization escapes. Together, our results rationalized a
new RBD epitope that leads to high neutralization potency and demonstrated
BD-368-2's therapeutic potential in treating COVID-19.
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