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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | Prefusion RSV F Bound to Lonafarnib and D25 Fab | |||||||||
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Function / homology | ![]() positive regulation of syncytium formation by virus / Translation of respiratory syncytial virus mRNAs / Assembly and release of respiratory syncytial virus (RSV) virions / Respiratory syncytial virus (RSV) attachment and entry / RSV-host interactions / Maturation of hRSV A proteins / host cell Golgi membrane / ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Yang Q / Xue B / Liu F / Peng W / Chen X | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Farnesyltransferase inhibitor lonafarnib suppresses respiratory syncytial virus infection by blocking conformational change of fusion glycoprotein. Authors: Qi Yang / Bao Xue / Fengjiang Liu / Yongzhi Lu / Jielin Tang / Mengrong Yan / Qiong Wu / Ruyi Chen / Anqi Zhou / Lijie Liu / Junjun Liu / Changbin Qu / Qingxin Wu / Muqing Fu / Jiayi Zhong / ...Authors: Qi Yang / Bao Xue / Fengjiang Liu / Yongzhi Lu / Jielin Tang / Mengrong Yan / Qiong Wu / Ruyi Chen / Anqi Zhou / Lijie Liu / Junjun Liu / Changbin Qu / Qingxin Wu / Muqing Fu / Jiayi Zhong / Jianwei Dong / Sijie Chen / Fan Wang / Yuan Zhou / Jie Zheng / Wei Peng / Jinsai Shang / Xinwen Chen / ![]() Abstract: Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children and the elderly. There are currently no approved RSV-specific therapeutic small molecules ...Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children and the elderly. There are currently no approved RSV-specific therapeutic small molecules available. Using high-throughput antiviral screening, we identified an oral drug, the prenylation inhibitor lonafarnib, which showed potent inhibition of the RSV fusion process. Lonafarnib exhibited antiviral activity against both the RSV A and B genotypes and showed low cytotoxicity in HEp-2 and human primary bronchial epithelial cells (HBEC). Time-of-addition and pseudovirus assays demonstrated that lonafarnib inhibits RSV entry, but has farnesyltransferase-independent antiviral efficacy. Cryo-electron microscopy revealed that lonafarnib binds to a triple-symmetric pocket within the central cavity of the RSV F metastable pre-fusion conformation. Mutants at the RSV F sites interacting with lonafarnib showed resistance to lonafarnib but remained fully sensitive to the neutralizing monoclonal antibody palivizumab. Furthermore, lonafarnib dose-dependently reduced the replication of RSV in BALB/c mice. Collectively, lonafarnib could be a potential fusion inhibitor for RSV infection. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 204 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17.3 KB 17.3 KB | Display Display | ![]() |
Images | ![]() | 20.2 KB | ||
Filedesc metadata | ![]() | 6.1 KB | ||
Others | ![]() ![]() | 200.2 MB 200.2 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8kg5MC 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
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.73 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_37210_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_37210_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Prefusion RSV F Bound to Lonafarnib and D25 Fab
Entire | Name: Prefusion RSV F Bound to Lonafarnib and D25 Fab |
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Components |
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-Supramolecule #1: Prefusion RSV F Bound to Lonafarnib and D25 Fab
Supramolecule | Name: Prefusion RSV F Bound to Lonafarnib and D25 Fab / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Fusion glycoprotein F0,Fibritin
Macromolecule | Name: Fusion glycoprotein F0,Fibritin / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 64.530602 KDa |
Recombinant expression | Organism: ![]() ![]() |
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 FIRKSDELLG SGYIPEAPRD GQAYVRKDGE WVFLSTFLSG LEVLFQGPGG WSHPQF EKG GGSGGGSGGS AWSHPQFEKG GS UniProtKB: Fusion glycoprotein F0, Fibritin |
-Macromolecule #2: D25 heavy chain
Macromolecule | Name: D25 heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 24.504629 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: QVQLVQSGAE VKKPGSSVMV SCQASGGPLR NYIINWLRQA PGQGPEWMGG IIPVLGTVHY APKFQGRVTI TADESTDTAY IHLISLRSE DTAMYYCATE TALVVSTTYL PHYFDNWGQG TLVTVSSAST KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF P EPVTVSWN ...String: QVQLVQSGAE VKKPGSSVMV SCQASGGPLR NYIINWLRQA PGQGPEWMGG IIPVLGTVHY APKFQGRVTI TADESTDTAY IHLISLRSE DTAMYYCATE TALVVSTTYL PHYFDNWGQG TLVTVSSAST KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF P EPVTVSWN SGALTSGVHT FPAVLQSSGL YSLSSVVTVP SSSLGTQTYI CNVNHKPSNT KVDKKVEPKS CDK |
-Macromolecule #3: D25 light chain
Macromolecule | Name: D25 light chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 23.325865 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: DIQMTQSPSS LSAAVGDRVT ITCQASQDIV NYLNWYQQKP GKAPKLLIYV ASNLETGVPS RFSGSGSGTD FSLTISSLQP EDVATYYCQ QYDNLPLTFG GGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String: DIQMTQSPSS LSAAVGDRVT ITCQASQDIV NYLNWYQQKP GKAPKLLIYV ASNLETGVPS RFSGSGSGTD FSLTISSLQP EDVATYYCQ QYDNLPLTFG GGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC |
-Macromolecule #4: 4-{2-[4-(3,10-DIBROMO-8-CHLORO-6,11-DIHYDRO-5H-BENZO[5,6]CYCLOHEP...
Macromolecule | Name: 4-{2-[4-(3,10-DIBROMO-8-CHLORO-6,11-DIHYDRO-5H-BENZO[5,6]CYCLOHEPTA[1,2-B]PYRIDIN-11-YL)PIPERIDIN-1-YL]-2-OXOETHYL}PIPERIDINE-1-CARBOXAMIDE type: ligand / ID: 4 / Number of copies: 3 / Formula: 336 |
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Molecular weight | Theoretical: 638.822 Da |
Chemical component information | ![]() ChemComp-336: |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: INSILICO MODEL |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.17 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 37059 |