National Natural Science Foundation of China (NSFC)
31971123
China
Citation
Journal: Cell Discov / Year: 2022 Title: Broad ultra-potent neutralization of SARS-CoV-2 variants by monoclonal antibodies specific to the tip of RBD. Authors: Hang Ma / Yingying Guo / Haoneng Tang / Chien-Te K Tseng / Lei Wang / Huifang Zong / Zhenyu Wang / Yang He / Yunsong Chang / Shusheng Wang / Haiqiu Huang / Yong Ke / Yunsheng Yuan / Mingyuan ...Authors: Hang Ma / Yingying Guo / Haoneng Tang / Chien-Te K Tseng / Lei Wang / Huifang Zong / Zhenyu Wang / Yang He / Yunsong Chang / Shusheng Wang / Haiqiu Huang / Yong Ke / Yunsheng Yuan / Mingyuan Wu / Yuanyuan Zhang / Aleksandra Drelich / Kempaiah Rayavara Kempaiah / Bi-Hung Peng / Ailin Wang / Kaiyong Yang / Haiyang Yin / Junjun Liu / Yali Yue / Wenbo Xu / Shuangli Zhu / Tianjiao Ji / Xiaoju Zhang / Ziqi Wang / Gang Li / Guangchun Liu / Jingjing Song / Lingling Mu / ZongShang Xiang / Zhangyi Song / Hua Chen / Yanlin Bian / Baohong Zhang / Hui Chen / Jiawei Zhang / Yunji Liao / Li Zhang / Li Yang / Yi Chen / John Gilly / Xiaodong Xiao / Lei Han / Hua Jiang / Yueqing Xie / Qiang Zhou / Jianwei Zhu / Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) continue to wreak havoc across the globe. Higher transmissibility and immunologic resistance of VOCs bring ...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) continue to wreak havoc across the globe. Higher transmissibility and immunologic resistance of VOCs bring unprecedented challenges to epidemic extinguishment. Here we describe a monoclonal antibody, 2G1, that neutralizes all current VOCs and has surprising tolerance to mutations adjacent to or within its interaction epitope. Cryo-electron microscopy structure showed that 2G1 bound to the tip of receptor binding domain (RBD) of spike protein with small contact interface but strong hydrophobic effect, which resulted in nanomolar to sub-nanomolar affinities to spike proteins. The epitope of 2G1 on RBD partially overlaps with angiotensin converting enzyme 2 (ACE2) interface, which enables 2G1 to block interaction between RBD and ACE2. The narrow binding epitope but high affinity bestow outstanding therapeutic efficacy upon 2G1 that neutralized VOCs with sub-nanomolar half maximal inhibitory concentration in vitro. In SARS-CoV-2, Beta or Delta variant-challenged transgenic mice and rhesus macaque models, 2G1 protected animals from clinical illness and eliminated viral burden, without serious impact to animal safety. Mutagenesis experiments suggest that 2G1 is potentially capable of dealing with emerging SARS-CoV-2 variants in the future. This report characterized the therapeutic antibodies specific to the tip of spike against SARS-CoV-2 variants and highlights the potential clinical applications as well as for developing vaccine and cocktail therapy.
History
Deposition
Feb 21, 2022
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Header (metadata) release
Mar 9, 2022
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Map release
Mar 9, 2022
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Update
Mar 9, 2022
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Current status
Mar 9, 2022
Processing site: PDBj / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
#259 - Jul 2021 Designed Proteins and Citizen Science similarity (1)
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Map
File
Download / File: emd_32921.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel size
X=Y=Z: 1.087 Å
Density
Contour Level
By AUTHOR: 0.035 / Movie #1: 0.035
Minimum - Maximum
-0.065312736 - 0.13791999
Average (Standard dev.)
2.7062646e-05 (±0.0023424614)
Symmetry
Space group: 1
Details
EMDB XML:
Map geometry
Axis order
X
Y
Z
Origin
0
0
0
Dimensions
288
288
288
Spacing
288
288
288
Cell
A=B=C: 313.056 Å α=β=γ: 90.0 °
CCP4 map header:
mode
Image stored as Reals
Å/pix. X/Y/Z
1.087
1.087
1.087
M x/y/z
288
288
288
origin x/y/z
0.000
0.000
0.000
length x/y/z
313.056
313.056
313.056
α/β/γ
90.000
90.000
90.000
start NX/NY/NZ
0
0
0
NX/NY/NZ
330
330
330
MAP C/R/S
1
2
3
start NC/NR/NS
0
0
0
NC/NR/NS
288
288
288
D min/max/mean
-0.065
0.138
0.000
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Supplemental data
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Sample components
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Entire : S protein of SARS-CoV-2 in complex with 2G1 focused on RBD_2G1 su...
Entire
Name: S protein of SARS-CoV-2 in complex with 2G1 focused on RBD_2G1 sub-complex
Components
Complex: S protein of SARS-CoV-2 in complex with 2G1 focused on RBD_2G1 sub-complex
Complex: S protein of SARS-CoV-2
Complex: 2G1
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Supramolecule #1: S protein of SARS-CoV-2 in complex with 2G1 focused on RBD_2G1 su...
Supramolecule
Name: S protein of SARS-CoV-2 in complex with 2G1 focused on RBD_2G1 sub-complex type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
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Supramolecule #2: S protein of SARS-CoV-2
Supramolecule
Name: S protein of SARS-CoV-2 / type: complex / Chimera: Yes / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)
Organism: Severe acute respiratory syndrome coronavirus
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