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Yorodumi- EMDB-64738: Cryo-EM structure of RSV pre-F trimer in complex with CNR2056/CNR2047 -
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Basic information
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| Title | Cryo-EM structure of RSV pre-F trimer in complex with CNR2056/CNR2047 | |||||||||
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Keywords | RSV / Fusion Protein / Antibody / VIRAL PROTEIN | |||||||||
| Biological species | Respiratory syncytial virus A2 / Homo sapiens (human) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 4.4 Å | |||||||||
Authors | Zhai H / Deng J / Yu W | |||||||||
| Funding support | 1 items
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Citation | Journal: Sci Transl Med / Year: 2026Title: Antibody cocktails based on the occupationally acquired immunity of pediatricians neutralize and confer protection against RSV and hMPV. Authors: Hui Zhai / Wenxiang Yu / Jinyue Wang / Jie Deng / Siyu Lei / Teng Zhou / Yixin Li / Kaijun Xu / Mengyang Ma / Rui Feng / Yaling Hu / Luo Ren / Yunlong Cao / Enmei Liu / Xiangxi Wang / ![]() Abstract: Human respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are major causes of severe respiratory infections in young children, older adults, and immunocompromised individuals. Here, we ...Human respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are major causes of severe respiratory infections in young children, older adults, and immunocompromised individuals. Here, we isolated RSV fusion (F) protein-specific B cells from pediatricians who are routinely exposed to these viruses. We then derived monoclonal antibodies (mAbs) from those B cells to characterize their binding and neutralization profiles. Among the isolated mAbs, we found that CNR2056 and CNR2053 (targeting site Ø of the pre-F protein) potently neutralized diverse RSV A and B strains; another mAb, CNR2047 (targeting site III), uniquely exhibited cross-neutralization capacity against both RSV and hMPV variants. In vivo, prophylactic administration of CNR2056 and CNR2053 controlled lung viral loads and pathology in RSV A2- and B9320-challenged cotton rats. Moreover, a prophylactic dose of 0.5 milligrams per kilogram of CNR2047 resulted in complete protection against hMPV in the lungs of BALB/c mice. Structural analysis revealed unique binding modes for the three mAbs, supporting the potential for rational mAb cocktail design. Deep mutational scanning for RSV F further demonstrated that mutations required to evade CNR2053 and CNR2056 were primarily in evolutionarily constrained sites, suggesting a fitness cost to immune escape. Rationally combining site Ø- and site III-directed mAbs (e.g., CNR2056-CNR2047) into cocktails conferred additive effects, expanding coverage to hMPV and minimizing risk of escape variants. Thus, rationally designed cocktails of CNR2056, CNR2053, and CNR2047 may offer a versatile immunoprophylactic agent against a range of pneumoviruses with potential to protect against both current and future variants. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_64738.map.gz | 97.3 MB | EMDB map data format | |
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| Header (meta data) | emd-64738-v30.xml emd-64738.xml | 24.5 KB 24.5 KB | Display Display | EMDB header |
| Images | emd_64738.png | 54.5 KB | ||
| Filedesc metadata | emd-64738.cif.gz | 6.6 KB | ||
| Others | emd_64738_half_map_1.map.gz emd_64738_half_map_2.map.gz | 95.6 MB 95.6 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-64738 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-64738 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9v2rMC ![]() 9v0nC ![]() 9v0pC ![]() 9v0qC ![]() 9v0sC ![]() 9v0tC ![]() 9v2oC ![]() 9v2qC M: atomic model generated by this map C: citing same article ( |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Map
| File | Download / File: emd_64738.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 1 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Half map: #2
| File | emd_64738_half_map_1.map | ||||||||||||
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-Half map: #1
| File | emd_64738_half_map_2.map | ||||||||||||
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| Density Histograms |
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Sample components
-Entire : RSV pre-F trimer in complex with CNR2056/CNR2047
| Entire | Name: RSV pre-F trimer in complex with CNR2056/CNR2047 |
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| Components |
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-Supramolecule #1: RSV pre-F trimer in complex with CNR2056/CNR2047
| Supramolecule | Name: RSV pre-F trimer in complex with CNR2056/CNR2047 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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| Source (natural) | Organism: Respiratory syncytial virus A2 |
-Supramolecule #2: RSV Pre-fusion Protein
| Supramolecule | Name: RSV Pre-fusion Protein / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #2 |
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| Source (natural) | Organism: Respiratory syncytial virus A2 |
-Supramolecule #3: Antibody CNR2056
| Supramolecule | Name: Antibody CNR2056 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #1, #3 |
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| Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #4: Antibody CNR2047
| Supramolecule | Name: Antibody CNR2047 / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #4-#5 |
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| Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: CNR2056 heavy chain
| Macromolecule | Name: CNR2056 heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 13.949546 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: QVQLVESGGG VVQPGTSLTL SCAASGFTFR TYAFHWVRQA PGKGLEWLAL VTYDGTTQYY ADSVKGRLTI YRDNSKNTLF LHLNSLRRD DTAIYFCARG GEGSFSWLGY LQYMDVWGQG TTVTVSS |
-Macromolecule #2: RSV Pre-fusion Protein
| Macromolecule | Name: RSV Pre-fusion Protein / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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| Source (natural) | Organism: Respiratory syncytial virus A2 |
| Molecular weight | Theoretical: 61.626539 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: MELLILKANA ITTILTAVTF CFASGQNITE EFYQSTCSAV SKGYLSALRT GWYTSVITIE LSNIKENKCN GTDAKVKLIK QELDKYKNA VTELQLLMQS TPATNNRARR ELPRFMNYTL NNAKKTNVTL SKKRKRRFLG FLLGVGSAIA SGVAVCKVLH L EGEVNKIK ...String: MELLILKANA ITTILTAVTF CFASGQNITE EFYQSTCSAV SKGYLSALRT GWYTSVITIE LSNIKENKCN GTDAKVKLIK QELDKYKNA VTELQLLMQS TPATNNRARR ELPRFMNYTL NNAKKTNVTL SKKRKRRFLG FLLGVGSAIA SGVAVCKVLH L EGEVNKIK SALLSTNKAV VSLSNGVSVL TFKVLDLKNY IDKQLLPILN KQSCSISNIE TVIEFQQKNN RLLEITREFS VN AGVTTPV STYMLTNSEL LSLINDMPIT NDQKKLMSNN VQIVRQQSYS IMCIIKEEVL AYVVQLPLYG VIDTPCWKLH TSP LCTTNT KEGSNICLTR TDRGWYCDNA GSVSFFPQAE TCKVQSNRVF CDTMNSLTLP SEVNLCNVDI FNPKYDCKIM TSKT DVSSS VITSLGAIVS CYGKTKCTAS NKNRGIIKTF SNGCDYVSNK GVDTVSVGNT LYYVNKQEGK SLYVKGEPII NFYDP LVFP SDEFDASISQ VNEKINQSLA FIRKSDELLS AIGGYIPEAP RDGQAYVRKD GEWVLLSTFL GHHHHHHHH |
-Macromolecule #3: CNR2056 light chain
| Macromolecule | Name: CNR2056 light chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 11.61957 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: QSALTQPASV SGSPGQSITL SCTGTSSDIG DYDYVSWYQK YPDTAPKLVI YDVSERPSGV STRFSGSKSG NTASLTISGL QPEDEADYY CNSYSSTNTL KFGGGTKLTV L |
-Macromolecule #4: CNR2047 heavy chain
| Macromolecule | Name: CNR2047 heavy chain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 12.947601 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: VQLVESGGGL VKPGESLRLS CAVSGSMFSS YVMHWVRQAP GKGLDWVSSI TGGGNYISYA DSVKGRFIIS RDNGRNSLSL QMSSLRVDD TAVYYCVRGL SGVMGVTWFD SWGQGTLVTV SS |
-Macromolecule #5: CNR2047 light chain
| Macromolecule | Name: CNR2047 light chain / type: protein_or_peptide / ID: 5 / Number of copies: 3 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 11.717903 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: QSVLTQPPSV SGAPGQRVTI SCTGSSSNIG AGFDVHWYQH LPGKAPKVII YENSHRPSGV PDRFFGSKSG TSASLSISGL QPEDEADYY CQSYDRGLDW VFGGGTKLTV L |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | 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 TECNAI ARCTICA |
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| Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 60.0 e/Å2 |
| Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: DARK FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.2 µm |
| Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Keywords
Respiratory syncytial virus A2
Homo sapiens (human)
Authors
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Processing
FIELD EMISSION GUN

