Journal: MedComm (2020) / Year: 2021 Title: Potent neutralizing RBD-specific antibody cocktail against SARS-CoV-2 and its mutant. Authors: Lina Jia / Yan-Ping Liu / Li-Fei Tian / Chao Xiong / Xin Xu / Honge Qu / Weixi Xiong / Dong Zhou / Feng Wang / Zheng Liu / Xiao-Xue Yan / Wenqing Xu / Lin Tang / Abstract: The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants has posed a serious global public health emergency. Therapeutic interventions or vaccines ...The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants has posed a serious global public health emergency. Therapeutic interventions or vaccines are urgently needed to treat and prevent the further dissemination of this contagious virus. This study described the identification of neutralizing receptor-binding domain (RBD)-specific antibodies from mice through vaccination with a recombinant SARS-CoV-2 RBD. RBD-targeted monoclonal antibodies (mAbs) with distinct function and epitope recognition were selected to understand SARS-CoV-2 neutralization. High-affinity RBD-specific antibodies exhibited high potency in neutralizing both live and pseudotype SARS-CoV-2 viruses and the SARS-CoV-2 pseudovirus particle containing the spike protein S-RBD mutant (SARS-CoV-2(V367F)). These results demonstrated that these antibodies recognize four distinct groups (I-IV) of epitopes on the RBD and that mAbs targeting group I epitope can be used in combination with mAbs recognizing groups II and/or IV epitope to make mAb cocktails against SARS-CoV-2 and its mutants. Moreover, structural characterization reveals that groups I, III, and IV epitopes are closely located to an RBD hotspot. The identification of RBD-specific antibodies and cocktails may provide an effective therapeutic and prophylactic intervention against SARS-CoV-2 and its isolates.
History
Deposition
Jan 7, 2021
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Header (metadata) release
Nov 17, 2021
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Map release
Nov 17, 2021
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Update
Nov 17, 2021
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Current status
Nov 17, 2021
Processing site: PDBj / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
Cryogen name: ETHANE / Details: blot for 5 seconds before plunging.
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Electron microscopy
Microscope
FEI TITAN KRIOS
Image recording
Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Number real images: 2265 / Average electron dose: 58.44 e/Å2 / Details: Preliminary grid screening was performed manually.
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron optics
Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
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Image processing
CTF correction
Software - Name: RELION
Final reconstruction
Resolution.type: BY AUTHOR / Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 116393
Initial angle assignment
Type: OTHER
Final angle assignment
Type: OTHER
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