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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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PDB id:
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| Name: |
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Protein binding/immune system
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Title:
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Crystal structure of the sars-cov-2 s rbd in complex with bd-604 fab
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Structure:
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Bd-604 fab h. Chain: h. Engineered: yes. Bd-604 fab l. Chain: l. Engineered: yes. Spike protein s1. Chain: r. Synonym: s glycoprotein,e2,peplomer protein,spike glycoprotein.
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Source:
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Homo sapiens. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: 293f. Severe acute respiratory syndrome coronavirus 2. 2019-ncov. Organism_taxid: 2697049.
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Resolution:
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3.15Å
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R-factor:
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0.228
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R-free:
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0.273
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Authors:
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S.Du,J.Y.Xiao
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Key ref:
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S.Du
et al.
(2020).
Structurally Resolved SARS-CoV-2 Antibody Shows High Efficacy in Severely Infected Hamsters and Provides a Potent Cocktail Pairing Strategy.
Cell,
183,
1013.
PubMed id:
DOI:
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Date:
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05-Jul-20
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Release date:
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16-Sep-20
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PROCHECK
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Headers
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References
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No UniProt id for this chain
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DOI no:
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Cell
183:1013
(2020)
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PubMed id:
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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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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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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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Links
