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Yorodumi- EMDB-33347: Cryo-EM structure of S glycoprotein encoded by the Covid-19 mRNA ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-33347 | ||||||||||||
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Title | Cryo-EM structure of S glycoprotein encoded by the Covid-19 mRNA vaccine candidate RQ3013 (Postfusion state) | ||||||||||||
Map data | |||||||||||||
Sample |
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Keywords | Spike / mRNA vaccine / SARS-CoV-2 / S clycoprotein / VIRAL PROTEIN | ||||||||||||
Function / homology | Function and homology information 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 | Severe acute respiratory syndrome coronavirus / synthetic construct (others) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||||||||
Authors | Wu Z / Yu Z / Tan S / Lu J / Lu G / Lin J | ||||||||||||
Funding support | China, 3 items
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Citation | Journal: Sci Bull (Beijing) / Year: 2023 Title: Preclinical evaluation of RQ3013, a broad-spectrum mRNA vaccine against SARS-CoV-2 variants. Authors: Shudan Tan / Jinghua Zhao / Xue Hu / Yufeng Li / Zihan Wu / Guoliang Lu / Zhaoli Yu / Binhe Du / Yan Liu / Li Li / Yuchen Chen / Ye Li / Yanfeng Yao / Xiaoyu Zhang / Juhong Rao / Ge Gao / ...Authors: Shudan Tan / Jinghua Zhao / Xue Hu / Yufeng Li / Zihan Wu / Guoliang Lu / Zhaoli Yu / Binhe Du / Yan Liu / Li Li / Yuchen Chen / Ye Li / Yanfeng Yao / Xiaoyu Zhang / Juhong Rao / Ge Gao / Yun Peng / Hang Liu / Zhiming Yuan / Jia Liu / Qianran Wang / Hengrui Hu / Xiaobo Gao / Hui Zhou / Hang Yu / Yingjie Xu / Wei Yu / Lin Feng / Manli Wang / Chao Shan / Jing Lu / Jinzhong Lin / Abstract: The global emergence of SARS-CoV-2 variants has led to increasing breakthrough infections in vaccinated populations, calling for an urgent need to develop more effective and broad-spectrum vaccines ...The global emergence of SARS-CoV-2 variants has led to increasing breakthrough infections in vaccinated populations, calling for an urgent need to develop more effective and broad-spectrum vaccines to combat COVID-19. Here we report the preclinical development of RQ3013, an mRNA vaccine candidate intended to bring broad protection against SARS-CoV-2 variants of concern (VOCs). RQ3013, which contains pseudouridine-modified mRNAs formulated in lipid nanoparticles, encodes the spike (S) protein harboring a combination of mutations responsible for immune evasion of VOCs. Here we characterized the expressed S immunogen and evaluated the immunogenicity, efficacy, and safety of RQ3013 in various animal models. RQ3013 elicited robust immune responses in mice, hamsters, and nonhuman primates (NHP). It can induce high titers of antibodies with broad cross-neutralizing ability against the wild-type, B.1.1.7, B.1.351, B.1.617.2, and the newly emerging Omicron variants. In mice and NHP, two doses of RQ3013 protected the upper and lower respiratory tract against infection by SARS-CoV-2 and its variants. Furthermore, our safety assessment of RQ3013 in NHP showed no observable adverse effects. These results provide strong support for the evaluation of RQ3013 in clinical trials and suggest that it may be a promising candidate for broad protection against COVID-19 and its variants. | ||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_33347.map.gz | 257.2 MB | EMDB map data format | |
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Header (meta data) | emd-33347-v30.xml emd-33347.xml | 16.8 KB 16.8 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_33347_fsc.xml | 17 KB | Display | FSC data file |
Images | emd_33347.png | 44.1 KB | ||
Masks | emd_33347_msk_1.map | 512 MB | Mask map | |
Filedesc metadata | emd-33347.cif.gz | 6.5 KB | ||
Others | emd_33347_half_map_1.map.gz emd_33347_half_map_2.map.gz | 475 MB 475 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33347 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33347 | HTTPS FTP |
-Validation report
Summary document | emd_33347_validation.pdf.gz | 1.2 MB | Display | EMDB validaton report |
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Full document | emd_33347_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | emd_33347_validation.xml.gz | 26.8 KB | Display | |
Data in CIF | emd_33347_validation.cif.gz | 35.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33347 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33347 | HTTPS FTP |
-Related structure data
Related structure data | 7xogMC 7xoeC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_33347.map.gz / Format: CCP4 / Size: 512 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: 1.1 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_33347_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_33347_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_33347_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Severe acute respiratory syndrome coronavirus
Entire | Name: Severe acute respiratory syndrome coronavirus |
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Components |
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-Supramolecule #1: Severe acute respiratory syndrome coronavirus
Supramolecule | Name: Severe acute respiratory syndrome coronavirus / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 Details: the full-length S glycoprotein encoded by the Covid-19 mRNA vaccine candidate RQ3013 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus / Strain: chimera strain |
-Macromolecule #1: Spike glycoprotein,peptide
Macromolecule | Name: Spike glycoprotein,peptide / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: synthetic construct (others) |
Molecular weight | Theoretical: 142.800703 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAISG TNGTKRFDNP VLPFNDGVY FASTEKSNII RGWIFGTTLD SKTQSLLIVN NATNVVIKVC EFQFCNDPFL GVYHKNNKSW MESEFRVYSS A NNCTFEYV ...String: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHAISG TNGTKRFDNP VLPFNDGVY FASTEKSNII RGWIFGTTLD SKTQSLLIVN NATNVVIKVC EFQFCNDPFL GVYHKNNKSW MESEFRVYSS A NNCTFEYV SQPFLMDLEG KQGNFKNLRE FVFKNIDGYF KIYSKHTPIN LVRDLPQGFS ALEPLVDLPI GINITRFQTL LA LHRSYLT PGDSSSGWTA GAAAYYVGYL QPRTFLLKYN ENGTITDAVD CALDPLSETK CTLKSFTVEK GIYQTSNFRV QPT ESIVRF PNITNLCPFG EVFNATRFAS VYAWNRKRIS NCVADYSVLY NSASFSTFKC YGVSPTKLND LCFTNVYADS FVIR GDEVR QIAPGQTGNI ADYNYKLPDD FTGCVIAWNS NNLDSKVGGN YNYLYRLFRK SNLKPFERDI STEIYQAGST PCNGV KGFN CYFPLQSYGF QPTYGVGYQP YRVVVLSFEL LHAPATVCGP KKSTNLVKNK CVNFNFNGLT GTGVLTESNK KFLPFQ QFG RDIDDTTDAV RDPQTLEILD ITPCSFGGVS VITPGTNTSN QVAVLYQGVN CTEVPVAIHA DQLTPTWRVY STGSNVF QT RAGCLIGAEH VNNSYECDIP IGAGICASYQ TQTNSHGSAS SVASQSIIAY TMSLGVENSV AYSNNSIAIP TNFTISVT T EILPVSMTKT SVDCTMYICG DSTECSNLLL QYGSFCTQLN RALTGIAVEQ DKNTQEVFAQ VKQIYKTPPI KDFGGFNFS QILPDPSKPS KRSFIEDLLF NKVTLADAGF IKQYGDCLGD IAARDLICAQ KFNGLTVLPP LLTDEMIAQY TSALLAGTIT SGWTFGAGA ALQIPFAMQM AYRFNGIGVT QNVLYENQKL IANQFNSAIG KIQDSLSSTA SALGKLQDVV NQNAQALNTL V KQLSSNFG AISSVLNDIL SRLDKVEAEV QIDRLITGRL QSLQTYVTQQ LIRAAEIRAS ANLAATKMSE CVLGQSKRVD FC GKGYHLM SFPQSAPHGV VFLHVTYVPA QEKNFTTAPA ICHDGKAHFP REGVFVSNGT HWFVTQRNFY EPQIITTDNT FVS GNCDVV IGIVNNTVYD PLQPELDSFK EELDKYFKNH TSPDVDLGDI SGINASVVNI QKEIDRLNEV AKNLNESLID LQEL GKYEQ YIKWPWYIWL GFIAGLIAIV MVTIMLCCMT SCCSCLKGCC SCGSCCKGSL EVLFQGPSGS WSHPQFEKGG GSGGG SGGS AWSHPQFEK UniProtKB: Spike glycoprotein |
-Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 9 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Macromolecule #6: alpha-D-mannopyranose
Macromolecule | Name: alpha-D-mannopyranose / type: ligand / ID: 6 / Number of copies: 3 / Formula: MAN |
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Molecular weight | Theoretical: 180.156 Da |
Chemical component information | ChemComp-MAN: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TECNAI ARCTICA |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 1.25 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 5.0 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |