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- EMDB-32654: The local refined map of Omicron spike with bispecific antibody FD01 -
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Open data
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Basic information
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Title | The local refined map of Omicron spike with bispecific antibody FD01 | |||||||||
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Function / homology | ![]() Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell ...Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated endocytosis of virus by host cell / membrane fusion / Attachment and Entry / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / symbiont-mediated suppression of host innate immune response / host cell surface receptor binding / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / identical protein binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.51 Å | |||||||||
![]() | Zhang X / Zhan WQ / Chen ZG / Sun L | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Combating the SARS-CoV-2 Omicron (BA.1) and BA.2 with potent bispecific antibodies engineered from non-Omicron neutralizing antibodies. Authors: Yingdan Wang / Xiang Zhang / Yunping Ma / Yanqun Wang / Wuqiang Zhan / Qinwen Zheng / Meng Zhang / Ping Ji / Mei Liu / Qianying Liu / Tingting Sun / Tongyu Zhu / Yumei Wen / Lei Sun / Jincun ...Authors: Yingdan Wang / Xiang Zhang / Yunping Ma / Yanqun Wang / Wuqiang Zhan / Qinwen Zheng / Meng Zhang / Ping Ji / Mei Liu / Qianying Liu / Tingting Sun / Tongyu Zhu / Yumei Wen / Lei Sun / Jincun Zhao / Fan Wu / Zhenguo Chen / Jinghe Huang / ![]() Abstract: The highly mutated and transmissible Omicron (BA.1) and its more contagious lineage BA.2 have provoked serious concerns over their decreased sensitivity to the current COVID-19 vaccines and evasion ...The highly mutated and transmissible Omicron (BA.1) and its more contagious lineage BA.2 have provoked serious concerns over their decreased sensitivity to the current COVID-19 vaccines and evasion from most anti-SARS-CoV-2 neutralizing antibodies (NAbs). In this study, we explored the possibility of combating the Omicron and BA.2 by constructing bispecific antibodies based on non-Omicron NAbs. We engineered 10 IgG-like bispecific antibodies with non-Omicron NAbs named GW01, 16L9, 4L12, and REGN10987 by fusing the single-chain variable fragments (scFvs) of two antibodies through a linker and then connecting them to the Fc region of IgG1. Surprisingly, 8 out of 10 bispecific antibodies showed high binding affinities to the Omicron receptor-binding domain (RBD) and exhibited extreme breadth and potency against pseudotyped SARS-CoV-2 variants of concern (VOCs) including Omicron and BA.2, with geometric mean of 50% inhibitory concentration (GM IC) values ranging from 4.5 ng/mL to 103.94 ng/mL, as well as the authentic BA.1.1. Six bispecific antibodies containing the cross-NAb GW01 not only neutralized Omicron and BA.2, but also neutralized the sarbecoviruses including SARS-CoV and SARS-related coronaviruses (SARSr-CoVs) RS3367 and WIV1, with GM IC ranging from 11.6 ng/mL to 103.9 ng/mL. Mapping analyses of 42 spike (S) variant single mutants of Omicron and BA.2 elucidated that these bispecific antibodies accommodated the S371L/F mutations, which were resistant to most of the non-Omicron NAbs. A cryo-electron microscopy (cryo-EM) structure study of the representative bispecific antibody GW01-16L9 (FD01) in its native full-length IgG form in complex with the Omicron S trimer revealed 5 distinct trimers and one novel trimer dimer conformation. 16L9 scFv binds the receptor-binding motif (RBM), while GW01 scFv binds a epitope outside the RBM. Two scFvs of the bispecific antibody synergistically induced the RBD-down conformation into 3 RBD-up conformation, improved the affinity between IgG and the Omicron RBD, induced the formation of trimer dimer, and inhibited RBD binding to ACE2. The trimer dimer conformation might induce the aggregation of virions and contribute to the neutralization ability of FD01. These novel bispecific antibodies are strong candidates for the treatment and prevention of infection with the Omicron, BA.2, VOCs, and other sarbecoviruses. Engineering bispecific antibodies based on non-Omicron NAbs could turn the majority of NAbs into a powerful arsenal to aid the battle against the pandemic. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 111.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 13.1 KB 13.1 KB | Display Display | ![]() |
Images | ![]() | 27.6 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7wopMC ![]() 7woqC ![]() 7worC ![]() 7wosC ![]() 7wouC ![]() 7wovC ![]() 7wowC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.064 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : Omicron Spike with 16L9 and GW01
Entire | Name: Omicron Spike with 16L9 and GW01 |
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Components |
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-Supramolecule #1: Omicron Spike with 16L9 and GW01
Supramolecule | Name: Omicron Spike with 16L9 and GW01 / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: Omicron Spike
Supramolecule | Name: Omicron Spike / type: complex / Chimera: Yes / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
-Supramolecule #3: 16L9 and GW01
Supramolecule | Name: 16L9 and GW01 / type: complex / Chimera: Yes / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Spike protein S1
Macromolecule | Name: Spike protein S1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 22.523479 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: NITNLCPFDE VFNATRFASV YAWNRKRISN CVADYSVLYN LAPFFTFKCY GVSPTKLNDL CFTNVYADSF VIRGDEVRQI APGQTGNIA DYNYKLPDDF TGCVIAWNSN KLDSKVSGNY NYLYRLFRKS NLKPFERDIS TEIYQAGNKP CNGVAGFNCY F PLRSYSFR ...String: NITNLCPFDE VFNATRFASV YAWNRKRISN CVADYSVLYN LAPFFTFKCY GVSPTKLNDL CFTNVYADSF VIRGDEVRQI APGQTGNIA DYNYKLPDDF TGCVIAWNSN KLDSKVSGNY NYLYRLFRKS NLKPFERDIS TEIYQAGNKP CNGVAGFNCY F PLRSYSFR PTYGVGHQPY RVVVLSFELL HAPATVCGPK |
-Macromolecule #2: 16L9
Macromolecule | Name: 16L9 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 25.730025 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QSVLTQPPSA SGSPGQSVTI SCTGTSSDFG GYNSVSWYQQ HPGKAPKLMI YEVSKRPSGV PDRFSGSKSG NTASLTVSGL QAEDEADYY CSSYAGSNNF DVFGTGTKVT VLGGGGSGGG GSGGGGSEVQ LVESGGGLIQ PGGSLRLSCA ASGFTVSSNY M SWVRQAPG ...String: QSVLTQPPSA SGSPGQSVTI SCTGTSSDFG GYNSVSWYQQ HPGKAPKLMI YEVSKRPSGV PDRFSGSKSG NTASLTVSGL QAEDEADYY CSSYAGSNNF DVFGTGTKVT VLGGGGSGGG GSGGGGSEVQ LVESGGGLIQ PGGSLRLSCA ASGFTVSSNY M SWVRQAPG KGLEWVSVIY SGGSTYYADS VKGRFTISRD NSENTLYLQM NSLRAEDTAV YYCARGEIQP YYYYGMDVWG QG TTVTVSS |
-Macromolecule #3: GW01
Macromolecule | Name: GW01 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 26.186488 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QSVLTQPPSA SGTPGQRVTI SCSGSSSNIG SNTVNWYQQL PGTAPKLLIY SNNQRPSGVP DRFSGSKSGT SASLAISGLQ SEDEADYYC AAWDDSLNWV FGGGTKLTVL GGGGSGGGGS GGGGSEVQLV ESGGGVVQPG GSLRLSCAAS GFRFDDHAMH W VRQAPGKG ...String: QSVLTQPPSA SGTPGQRVTI SCSGSSSNIG SNTVNWYQQL PGTAPKLLIY SNNQRPSGVP DRFSGSKSGT SASLAISGLQ SEDEADYYC AAWDDSLNWV FGGGTKLTVL GGGGSGGGGS GGGGSEVQLV ESGGGVVQPG GSLRLSCAAS GFRFDDHAMH W VRQAPGKG LEWVSVISGD GGSTYYADSV KGRFSISRDD SKNSLYLQMN SLRTEDTALY YCAKDRSYGP PDVFNYEYGM DV WGQGTTV TVSS |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 58.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.51 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 249122 |
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Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |