Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) is a lineage C betacoronavirus that since its emergence in 2012 has caused outbreaks in human populations with case-fatality rates of ~36%. As in other coronaviruses, the spike (S) glycoprotein of MERS-CoV mediates receptor recognition and membrane fusion and is the primary target of the humoral immune response during infection. Here we use structure-based design to develop a generalizable strategy for retaining coronavirus S proteins in the antigenically optimal prefusion conformation and demonstrate that our engineered immunogen is able to elicit high neutralizing antibody titers against MERS-CoV. We also determined high-resolution structures of the trimeric MERS-CoV S ectodomain in complex with G4, a stem-directed neutralizing antibody. The structures reveal that G4 recognizes a glycosylated loop that is variable among coronaviruses and they define four conformational states of the trimer wherein each receptor-binding domain is either tightly packed at the membrane-distal apex or rotated into a receptor-accessible conformation. As a result, our studies suggest a potential mechanism for fusion initiation through sequential receptor-binding events and provide a foundation for the structure-based design of coronavirus vaccines.
- Authors:
-
[2]
- The Scripps Research Inst., La Jolla, CA (United States)
- Geisel School of Medicine at Dartmouth, Hanover, NH (United States)
- National Inst. of Allergy and Infectious Diseases, Bethesda, MD (United States)
- Vanderbilt Univ. Medical Center, Nashville, TN (United States)
- Geisel School of Medicine at Dartmouth, Hanover, NH (United States); Geisel School of Medicine at Dartmouth, Lebanon, NH (United States)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER); USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH); National Inst. of Allergy and Infectious Diseases; National Inst. of General Medical Sciences
- OSTI Identifier:
- 1390889
- Grant/Contract Number:
- AC02-06CH11357; AC02-76SF00515; R01AI127521; P20GM113132; HHSN261200800001E; P41GM103393
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Proceedings of the National Academy of Sciences of the United States of America
- Additional Journal Information:
- Journal Volume: 114; Journal Issue: 35; Journal ID: ISSN 0027-8424
- Publisher:
- National Academy of Sciences
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; coronavirus; neutralizing antibody; cryo-EM; X-ray; crystallography; peplomer
Citation Formats
Pallesen, Jesper, Wang, Nianshuang, Corbett, Kizzmekia S., Wrapp, Daniel, Kirchdoerfer, Robert N., Turner, Hannah L., Cottrell, Christopher A., Becker, Michelle M., Wang, Lingshu, Shi, Wei, Kong, Wing-Pui, Andres, Erica L., Kettenbach, Arminja N., Denison, Mark R., Chappell, James D., Graham, Barney S., Ward, Andrew B., and McLellan, Jason S. Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen. United States: N. p., 2017.
Web. doi:10.1073/pnas.1707304114.
Pallesen, Jesper, Wang, Nianshuang, Corbett, Kizzmekia S., Wrapp, Daniel, Kirchdoerfer, Robert N., Turner, Hannah L., Cottrell, Christopher A., Becker, Michelle M., Wang, Lingshu, Shi, Wei, Kong, Wing-Pui, Andres, Erica L., Kettenbach, Arminja N., Denison, Mark R., Chappell, James D., Graham, Barney S., Ward, Andrew B., & McLellan, Jason S. Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen. United States. https://doi.org/10.1073/pnas.1707304114
Pallesen, Jesper, Wang, Nianshuang, Corbett, Kizzmekia S., Wrapp, Daniel, Kirchdoerfer, Robert N., Turner, Hannah L., Cottrell, Christopher A., Becker, Michelle M., Wang, Lingshu, Shi, Wei, Kong, Wing-Pui, Andres, Erica L., Kettenbach, Arminja N., Denison, Mark R., Chappell, James D., Graham, Barney S., Ward, Andrew B., and McLellan, Jason S. Mon .
"Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen". United States. https://doi.org/10.1073/pnas.1707304114. https://www.osti.gov/servlets/purl/1390889.
@article{osti_1390889,
title = {Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen},
author = {Pallesen, Jesper and Wang, Nianshuang and Corbett, Kizzmekia S. and Wrapp, Daniel and Kirchdoerfer, Robert N. and Turner, Hannah L. and Cottrell, Christopher A. and Becker, Michelle M. and Wang, Lingshu and Shi, Wei and Kong, Wing-Pui and Andres, Erica L. and Kettenbach, Arminja N. and Denison, Mark R. and Chappell, James D. and Graham, Barney S. and Ward, Andrew B. and McLellan, Jason S.},
abstractNote = {Middle East respiratory syndrome coronavirus (MERS-CoV) is a lineage C betacoronavirus that since its emergence in 2012 has caused outbreaks in human populations with case-fatality rates of ~36%. As in other coronaviruses, the spike (S) glycoprotein of MERS-CoV mediates receptor recognition and membrane fusion and is the primary target of the humoral immune response during infection. Here we use structure-based design to develop a generalizable strategy for retaining coronavirus S proteins in the antigenically optimal prefusion conformation and demonstrate that our engineered immunogen is able to elicit high neutralizing antibody titers against MERS-CoV. We also determined high-resolution structures of the trimeric MERS-CoV S ectodomain in complex with G4, a stem-directed neutralizing antibody. The structures reveal that G4 recognizes a glycosylated loop that is variable among coronaviruses and they define four conformational states of the trimer wherein each receptor-binding domain is either tightly packed at the membrane-distal apex or rotated into a receptor-accessible conformation. As a result, our studies suggest a potential mechanism for fusion initiation through sequential receptor-binding events and provide a foundation for the structure-based design of coronavirus vaccines.},
doi = {10.1073/pnas.1707304114},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 35,
volume = 114,
place = {United States},
year = {Mon Aug 14 00:00:00 EDT 2017},
month = {Mon Aug 14 00:00:00 EDT 2017}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 568 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Glycan shield and epitope masking of a coronavirus spike protein observed by cryo-electron microscopy
journal, September 2016
- Walls, Alexandra C.; Tortorici, M. Alejandra; Frenz, Brandon
- Nature Structural & Molecular Biology, Vol. 23, Issue 10
Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein
journal, October 2014
- Millet, Jean Kaoru; Whittaker, Gary R.
- Proceedings of the National Academy of Sciences, Vol. 111, Issue 42
A humanized neutralizing antibody against MERS-CoV targeting the receptor-binding domain of the spike protein
journal, September 2015
- Li, Yan; Wan, Yuhua; Liu, Peipei
- Cell Research, Vol. 25, Issue 11
Broadening of Neutralization Activity to Directly Block a Dominant Antibody-Driven SARS-Coronavirus Evolution Pathway
journal, November 2008
- Sui, Jianhua; Aird, Daniel R.; Tamin, Azaibi
- PLoS Pathogens, Vol. 4, Issue 11
Accurate determination of local defocus and specimen tilt in electron microscopy
journal, June 2003
- Mindell, Joseph A.; Grigorieff, Nikolaus
- Journal of Structural Biology, Vol. 142, Issue 3
Reverse genetics with a full-length infectious cDNA of the Middle East respiratory syndrome coronavirus
journal, September 2013
- Scobey, T.; Yount, B. L.; Sims, A. C.
- Proceedings of the National Academy of Sciences, Vol. 110, Issue 40
Crystal Structure of Bovine Coronavirus Spike Protein Lectin Domain
journal, October 2012
- Peng, Guiqing; Xu, Liqing; Lin, Yi-Lun
- Journal of Biological Chemistry, Vol. 287, Issue 50
Collaboration gets the most out of software
journal, September 2013
- Morin, Andrew; Eisenbraun, Ben; Key, Jason
- eLife, Vol. 2
Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM
journal, May 2013
- Li, Xueming; Mooney, Paul; Zheng, Shawn
- Nature Methods, Vol. 10, Issue 6
Atomic-accuracy models from 4.5-Å cryo-electron microscopy data with density-guided iterative local refinement
journal, February 2015
- DiMaio, Frank; Song, Yifan; Li, Xueming
- Nature Methods, Vol. 12, Issue 4
A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen
journal, August 2015
- Impagliazzo, A.; Milder, F.; Kuipers, H.
- Science, Vol. 349, Issue 6254
PHENIX : building new software for automated crystallographic structure determination
journal, October 2002
- Adams, Paul D.; Grosse-Kunstleve, Ralf W.; Hung, Li-Wei
- Acta Crystallographica Section D Biological Crystallography, Vol. 58, Issue 11
Two-Step Conformational Changes in a Coronavirus Envelope Glycoprotein Mediated by Receptor Binding and Proteolysis
journal, August 2009
- Matsuyama, S.; Taguchi, F.
- Journal of Virology, Vol. 83, Issue 21
X-Ray Diffraction data from MERS-CoV S2-specific Fab G4, source of 5VZR structure
dataset, January 2017
- Wang, Nianshuang
- SBGrid Data Bank
X-Ray Diffraction data from MERS-CoV S1 NTD, source of 5VYH structure
dataset, January 2017
- Wang, Nianshuang
- SBGrid Data Bank
Evidence for Camel-to-Human Transmission of MERS Coronavirus
journal, June 2014
- Azhar, Esam I.; El-Kafrawy, Sherif A.; Farraj, Suha A.
- New England Journal of Medicine, Vol. 370, Issue 26
Specific Single or Double Proline Substitutions in the “Spring-loaded” Coiled-Coil Region of the Influenza Hemagglutinin Impair or Abolish Membrane Fusion Activity
journal, June 1998
- Qiao, Hui; Pelletier, Sandra L.; Hoffman, Lucas
- The Journal of Cell Biology, Vol. 141, Issue 6
Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC
journal, March 2013
- Raj, V. Stalin; Mou, Huihui; Smits, Saskia L.
- Nature, Vol. 495, Issue 7440
Structure and immune recognition of trimeric pre-fusion HIV-1 Env
text, January 2014
- B., Munro, James; Lynn, Morris,; Tongqing, Zhou,
- The University of North Carolina at Chapel Hill University Libraries
Antibody Recognition of a Highly Conserved Influenza Virus Epitope
journal, April 2009
- Ekiert, D. C.; Bhabha, G.; Elsliger, M. -A.
- Science, Vol. 324, Issue 5924
Carbohydrate Structure Suite (CSS): analysis of carbohydrate 3D structures derived from the PDB
journal, December 2004
- Lutteke, T.
- Nucleic Acids Research, Vol. 33, Issue Database issue
Hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection
journal, August 2015
- Yassine, Hadi M.; Boyington, Jeffrey C.; McTamney, Patrick M.
- Nature Medicine, Vol. 21, Issue 9
Comparative Protein Structure Modeling Using MODELLER
journal, November 2016
- Webb, Benjamin; Sali, Andrej
- Current Protocols in Protein Science, Vol. 86, Issue 1
Human Monoclonal Antibody Combination against SARS Coronavirus: Synergy and Coverage of Escape Mutants
journal, July 2006
- ter Meulen, Jan; van den Brink, Edward N.; Poon, Leo L. M.
- PLoS Medicine, Vol. 3, Issue 7
Synthetic antibodies against BRIL as universal fiducial marks for single−particle cryoEM structure determination of membrane proteins
journal, March 2020
- Mukherjee, Somnath; Erramilli, Satchal K.; Ammirati, Mark
- Nature Communications, Vol. 11, Issue 1
The Spike Protein of the Emerging Betacoronavirus EMC Uses a Novel Coronavirus Receptor for Entry, Can Be Activated by TMPRSS2, and Is Targeted by Neutralizing Antibodies
journal, March 2013
- Gierer, S.; Bertram, S.; Kaup, F.
- Journal of Virology, Vol. 87, Issue 10
UCSF Chimera?A visualization system for exploratory research and analysis
journal, January 2004
- Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C.
- Journal of Computational Chemistry, Vol. 25, Issue 13
Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding
journal, December 2016
- Gui, Miao; Song, Wenfei; Zhou, Haixia
- Cell Research, Vol. 27, Issue 1
Vaccines against respiratory syncytial virus: The time has finally come
journal, June 2016
- Graham, Barney S.
- Vaccine, Vol. 34, Issue 30
Conformational dynamics of single HIV-1 envelope trimers on the surface of native virions
journal, October 2014
- Munro, J. B.; Gorman, J.; Ma, X.
- Science, Vol. 346, Issue 6210
MolProbity : all-atom structure validation for macromolecular crystallography
journal, December 2009
- Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J.
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1
Coronavirus as a possible cause of severe acute respiratory syndrome
journal, April 2003
- Peiris, Jsm; Lai, St; Poon, Llm
- The Lancet, Vol. 361, Issue 9366
Receptor-binding domain-based subunit vaccines against MERS-CoV
journal, April 2015
- Zhang, Naru; Tang, Jian; Lu, Lu
- Virus Research, Vol. 202
X-Ray Diffraction data from MERS-CoV S2-specific Fab G4, source of 5VZR structure
dataset, January 2017
- Wang, Nianshuang
- SBGrid Data Bank
Risk Factors for Primary Middle East Respiratory Syndrome Coronavirus Illness in Humans, Saudi Arabia, 2014
journal, January 2016
- Alraddadi, Basem M.; Watson, John T.; Almarashi, Abdulatif
- Emerging Infectious Diseases, Vol. 22, Issue 1
X-Ray Diffraction data from MERS-CoV S1 NTD, source of 5VYH structure
dataset, January 2017
- Wang, Nianshuang
- SBGrid Data Bank
Uncleaved prefusion-optimized gp140 trimers derived from analysis of HIV-1 envelope metastability
journal, June 2016
- Kong, Leopold; He, Linling; de Val, Natalia
- Nature Communications, Vol. 7, Issue 1
ConSurf 2016: an improved methodology to estimate and visualize evolutionary conservation in macromolecules
journal, May 2016
- Ashkenazy, Haim; Abadi, Shiran; Martz, Eric
- Nucleic Acids Research, Vol. 44, Issue W1
X-ray structure determination using low-resolution electron microscopy maps for molecular replacement
journal, July 2015
- Jackson, Ryan N.; McCoy, Airlie J.; Terwilliger, Thomas C.
- Nature Protocols, Vol. 10, Issue 9
Middle East Respiratory Syndrome: Emergence of a Pathogenic Human Coronavirus
journal, January 2017
- Fehr, Anthony R.; Channappanavar, Rudragouda; Perlman, Stanley
- Annual Review of Medicine, Vol. 68, Issue 1
HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites
journal, December 2002
- Kwong, Peter D.; Doyle, Michael L.; Casper, David J.
- Nature, Vol. 420, Issue 6916
Structure and immune recognition of trimeric pre-fusion HIV-1 Env
journal, October 2014
- Pancera, Marie; Zhou, Tongqing; Druz, Aliaksandr
- Nature, Vol. 514, Issue 7523
Isolation of a Novel Coronavirus from a Man with Pneumonia in Saudi Arabia
journal, November 2012
- Zaki, Ali M.; van Boheemen, Sander; Bestebroer, Theo M.
- New England Journal of Medicine, Vol. 367, Issue 19
DoG Picker and TiltPicker: Software tools to facilitate particle selection in single particle electron microscopy
journal, May 2009
- Voss, N. R.; Yoshioka, C. K.; Radermacher, M.
- Journal of Structural Biology, Vol. 166, Issue 2
Human Coronavirus HKU1 Spike Protein Uses O-Acetylated Sialic Acid as an Attachment Receptor Determinant and Employs Hemagglutinin-Esterase Protein as a Receptor-Destroying Enzyme
text, January 2015
- Qi, Yonghe; Dong, Wenjuan; Zhu, Quan K.
- American Society for Microbiology
Potent Neutralization of MERS-CoV by Human Neutralizing Monoclonal Antibodies to the Viral Spike Glycoprotein
journal, April 2014
- Jiang, L.; Wang, N.; Zuo, T.
- Science Translational Medicine, Vol. 6, Issue 234
Appion: An integrated, database-driven pipeline to facilitate EM image processing
journal, April 2009
- Lander, Gabriel C.; Stagg, Scott M.; Voss, Neil R.
- Journal of Structural Biology, Vol. 166, Issue 1
Identification of an Antigenic Determinant on the S2 Domain of the Severe Acute Respiratory Syndrome Coronavirus Spike Glycoprotein Capable of Inducing Neutralizing Antibodies
journal, June 2004
- Zhang, H.; Wang, G.; Li, J.
- Journal of Virology, Vol. 78, Issue 13
Automated molecular microscopy: The new Leginon system
journal, July 2005
- Suloway, Christian; Pulokas, James; Fellmann, Denis
- Journal of Structural Biology, Vol. 151, Issue 1
Structure-Based Design of a Fusion Glycoprotein Vaccine for Respiratory Syncytial Virus
journal, October 2013
- McLellan, J. S.; Chen, M.; Joyce, M. G.
- Science, Vol. 342, Issue 6158
A spring-loaded mechanism for the conformational change of influenza hemagglutinin
journal, May 1993
- Carr, Chavela M.; Kim, Peter S.
- Cell, Vol. 73, Issue 4
How good are my data and what is the resolution?
journal, June 2013
- Evans, Philip R.; Murshudov, Garib N.
- Acta Crystallographica Section D Biological Crystallography, Vol. 69, Issue 7
Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution
journal, April 2014
- Tang, X. -C.; Agnihothram, S. S.; Jiao, Y.
- Proceedings of the National Academy of Sciences, Vol. 111, Issue 19
Crystal Structure of a Soluble Cleaved HIV-1 Envelope Trimer
journal, October 2013
- Julien, J. -P.; Cupo, A.; Sok, D.
- Science, Vol. 342, Issue 6165
Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26
journal, July 2013
- Lu, Guangwen; Hu, Yawei; Wang, Qihui
- Nature, Vol. 500, Issue 7461
Cryo-EM Structure of a Fully Glycosylated Soluble Cleaved HIV-1 Envelope Trimer
journal, October 2013
- Lyumkis, D.; Julien, J. -P.; de Val, N.
- Science, Vol. 342, Issue 6165
Comparative Protein Structure Modeling Using MODELLER
journal, September 2014
- Webb, Benjamin; Sali, Andrej
- Current Protocols in Bioinformatics, Vol. 47, Issue 1
Structure, Function, and Evolution of Coronavirus Spike Proteins
journal, September 2016
- Li, Fang
- Annual Review of Virology, Vol. 3, Issue 1
Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp
journal, August 2014
- Qiu, Xiangguo; Wong, Gary; Audet, Jonathan
- Nature, Vol. 514, Issue 7520
Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus
journal, July 2015
- Corti, Davide; Zhao, Jincun; Pedotti, Mattia
- Proceedings of the National Academy of Sciences, Vol. 112, Issue 33
Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution
text, January 2014
- A., Marasco, Wayne; Jared, Sheehan,; L., Graham, Rachel
- The University of North Carolina at Chapel Hill University Libraries
Improved molecular replacement by density- and energy-guided protein structure optimization
journal, May 2011
- DiMaio, Frank; Terwilliger, Thomas C.; Read, Randy J.
- Nature, Vol. 473, Issue 7348
A roadmap for MERS-CoV research and product development: report from a World Health Organization consultation
journal, July 2016
- Modjarrad, Kayvon; Moorthy, Vasee S.; Ben Embarek, Peter
- Nature Medicine, Vol. 22, Issue 7
iMOSFLM : a new graphical interface for diffraction-image processing with MOSFLM
journal, March 2011
- Battye, T. Geoff G.; Kontogiannis, Luke; Johnson, Owen
- Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
The Buccaneer software for automated model building. 1. Tracing protein chains
journal, August 2006
- Cowtan, Kevin
- Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 9
Human Coronavirus HKU1 Spike Protein Uses O -Acetylated Sialic Acid as an Attachment Receptor Determinant and Employs Hemagglutinin-Esterase Protein as a Receptor-Destroying Enzyme
journal, April 2015
- Huang, Xingchuan; Dong, Wenjuan; Milewska, Aleksandra
- Journal of Virology, Vol. 89, Issue 14
Evaluation of candidate vaccine approaches for MERS-CoV
journal, July 2015
- Wang, Lingshu; Shi, Wei; Joyce, M. Gordon
- Nature Communications, Vol. 6, Issue 1
A single amino acid substitution in the S1 and S2 Spike protein domains determines the neutralization escape phenotype of SARS-CoV
journal, July 2008
- Mitsuki, Yu-ya; Ohnishi, Kazuo; Takagi, Hirotaka
- Microbes and Infection, Vol. 10, Issue 8
Privateer: software for the conformational validation of carbohydrate structures
journal, November 2015
- Agirre, Jon; Iglesias-Fernández, Javier; Rovira, Carme
- Nature Structural & Molecular Biology, Vol. 22, Issue 11
Sequential activation of the three protomers in the Moloney murine leukemia virus Env
journal, February 2017
- Sjöberg, Mathilda; Löving, Robin; Lindqvist, Birgitta
- Proceedings of the National Academy of Sciences, Vol. 114, Issue 10
Genomic Characterization of a Newly Discovered Coronavirus Associated with Acute Respiratory Distress Syndrome in Humans
journal, November 2012
- van Boheemen, Sander; de Graaf, Miranda; Lauber, Chris
- mBio, Vol. 3, Issue 6
Coronavirus Diversity, Phylogeny and Interspecies Jumping
journal, October 2009
- Woo, Patrick C. Y.; Lau, Susanna K. P.; Huang, Yi
- Experimental Biology and Medicine, Vol. 234, Issue 10
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) origin and animal reservoir
journal, June 2016
- Mohd, Hamzah A.; Al-Tawfiq, Jaffar A.; Memish, Ziad A.
- Virology Journal, Vol. 13, Issue 1
RELION: Implementation of a Bayesian approach to cryo-EM structure determination
journal, December 2012
- Scheres, Sjors H. W.
- Journal of Structural Biology, Vol. 180, Issue 3, p. 519-530
Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus
text, January 2015
- Barrett, Nicholas A.; Agnihothram, Sudhakar; Simonelli, Luca
- Proceedings of the National Academy of Sciences of the United States of America
EMRinger: side chain–directed model and map validation for 3D cryo-electron microscopy
journal, August 2015
- Barad, Benjamin A.; Echols, Nathaniel; Wang, Ray Yu-Ruei
- Nature Methods, Vol. 12, Issue 10
Middle East Respiratory Syndrome
journal, February 2017
- Arabi, Yaseen M.; Balkhy, Hanan H.; Hayden, Frederick G.
- New England Journal of Medicine, Vol. 376, Issue 6
Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody
journal, May 2016
- Kong, R.; Xu, K.; Zhou, T.
- Science, Vol. 352, Issue 6287
Topology representing network enables highly accurate classification of protein images taken by cryo electron-microscope without masking
journal, September 2003
- Ogura, Toshihiko; Iwasaki, Kenji; Sato, Chikara
- Journal of Structural Biology, Vol. 143, Issue 3
Refinement of Protein Structures into Low-Resolution Density Maps Using Rosetta
journal, September 2009
- DiMaio, Frank; Tyka, Michael D.; Baker, Matthew L.
- Journal of Molecular Biology, Vol. 392, Issue 1
Middle East Respiratory Syndrome Coronavirus Infection Mediated by the Transmembrane Serine Protease TMPRSS2
journal, September 2013
- Shirato, Kazuya; Kawase, Miyuki; Matsuyama, Shutoku
- Journal of Virology, Vol. 87, Issue 23
Reverse genetics with a full-length infectious cDNA of the Middle East respiratory syndrome coronavirus
text, January 2013
- Yount, Boyd L.; Menachery, Vineet D.; Graham, Rachel L.
- The University of North Carolina at Chapel Hill University Libraries
Enhancing Protein Crystallization through Precipitant Synergy
journal, September 2003
- Majeed, Shahzad; Ofek, Gilad; Belachew, Adam
- Structure, Vol. 11, Issue 9
Pre-fusion structure of a human coronavirus spike protein
journal, March 2016
- Kirchdoerfer, Robert N.; Cottrell, Christopher A.; Wang, Nianshuang
- Nature, Vol. 531, Issue 7592
Cryo-EM structure of a native, fully glycosylated, cleaved HIV-1 envelope trimer
journal, March 2016
- Lee, J. H.; Ozorowski, G.; Ward, A. B.
- Science, Vol. 351, Issue 6277
Quantitative phosphoproteomics reveals new roles for the protein phosphatase PP6 in mitotic cells
journal, October 2015
- Rusin, Scott F.; Schlosser, Kate A.; Adamo, Mark E.
- Science Signaling, Vol. 8, Issue 398
2015 MERS outbreak in Korea: hospital-to-hospital transmission
journal, January 2015
- Ki, Moran
- Epidemiology and Health, Vol. 37
Cryo-electron microscopy structure of a coronavirus spike glycoprotein trimer
journal, February 2016
- Walls, Alexandra C.; Tortorici, M. Alejandra; Bosch, Berend-Jan
- Nature, Vol. 531, Issue 7592
Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4
journal, July 2013
- Wang, Nianshuang; Shi, Xuanling; Jiang, Liwei
- Cell Research, Vol. 23, Issue 8
Coronavirus disease 2019 (COVID-19) can predispose young to Intracerebral hemorrhage: a retrospective observational study
journal, February 2021
- Lawton, Michael T.; Alimohammadi, Ehsan; Bagheri, Seyed Reza
- BMC Neurology, Vol. 21, Issue 1
Phaser crystallographic software
journal, July 2007
- McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
- Journal of Applied Crystallography, Vol. 40, Issue 4
Crystal structure of mouse coronavirus receptor-binding domain complexed with its murine receptor
journal, June 2011
- Peng, G.; Sun, D.; Rajashankar, K. R.
- Proceedings of the National Academy of Sciences, Vol. 108, Issue 26
A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism
journal, September 2015
- Krarup, Anders; Truan, Daphné; Furmanova-Hollenstein, Polina
- Nature Communications, Vol. 6, Issue 1
Identification of an immunodominant linear neutralization domain on the S2 portion of the murine coronavirus spike glycoprotein and evidence that it forms part of complex tridimensional structure.
journal, January 1993
- Daniel, C.; Anderson, R.; Buchmeier, M. J.
- Journal of Virology, Vol. 67, Issue 3
Cloning of the mouse hepatitis virus (MHV) receptor: expression in human and hamster cell lines confers susceptibility to MHV.
journal, January 1991
- Dveksler, G. S.; Pensiero, M. N.; Cardellichio, C. B.
- Journal of Virology, Vol. 65, Issue 12
Localization of neutralizing epitopes and the receptor-binding site within the amino-terminal 330 amino acids of the murine coronavirus spike protein.
journal, January 1994
- Kubo, H.; Yamada, Y. K.; Taguchi, F.
- Journal of Virology, Vol. 68, Issue 9
Works referencing / citing this record:
The use of databases, data mining and immunoinformatics in vaccinology: where are we?
journal, November 2017
- Hegde, Nagendra R.; Gauthami, S.; Sampath Kumar, H. M.
- Expert Opinion on Drug Discovery, Vol. 13, Issue 2
In silico screening of known small molecules to bind ACE2 specific RBD on Spike glycoprotein of SARS-CoV-2 for repurposing against COVID-19
journal, January 2020
- Br, Bharath; Damle, Hrishikesh; Ganju, Shiban
- F1000Research, Vol. 9
Structural basis for human coronavirus attachment to sialic acid receptors
journal, June 2019
- Tortorici, M. Alejandra; Walls, Alexandra C.; Lang, Yifei
- Nature Structural & Molecular Biology, Vol. 26, Issue 6
Trypsin Treatment Unlocks Barrier for Zoonotic Bat Coronavirus Infection
journal, December 2019
- Menachery, Vineet D.; Dinnon, Kenneth H.; Yount, Boyd L.
- Journal of Virology, Vol. 94, Issue 5
Prospects for a MERS-CoV spike vaccine
journal, August 2018
- Zhou, Yusen; Jiang, Shibo; Du, Lanying
- Expert Review of Vaccines, Vol. 17, Issue 8
Advances in MERS-CoV Vaccines and Therapeutics Based on the Receptor-Binding Domain
journal, January 2019
- Zhou, Yusen; Yang, Yang; Huang, Jingwei
- Viruses, Vol. 11, Issue 1
Structures of MERS-CoV spike glycoprotein in complex with sialoside attachment receptors
journal, December 2019
- Park, Young-Jun; Walls, Alexandra C.; Wang, Zhaoqian
- Nature Structural & Molecular Biology, Vol. 26, Issue 12
Superior immune responses induced by intranasal immunization with recombinant adenovirus-based vaccine expressing full-length Spike protein of Middle East respiratory syndrome coronavirus
journal, July 2019
- Kim, Myung Hee; Kim, Hyun Jik; Chang, Jun
- PLOS ONE, Vol. 14, Issue 7
Cryo-EM Studies of Virus-Antibody Immune Complexes
journal, January 2020
- Li, Na; Li, Zhiqiang; Fu, Yan
- Virologica Sinica, Vol. 35, Issue 1
Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein
journal, July 2019
- Zhou, Haixia; Chen, Yingzhu; Zhang, Shuyuan
- Nature Communications, Vol. 10, Issue 1
Middle East Respiratory Syndrome Vaccine Candidates: Cautious Optimism
journal, January 2019
- Schindewolf, Craig; Menachery, Vineet
- Viruses, Vol. 11, Issue 1
Global site-specific analysis of glycoprotein N-glycan processing
journal, May 2018
- Cao, Liwei; Diedrich, Jolene K.; Ma, Yuanhui
- Nature Protocols, Vol. 13, Issue 6
Comparative Serological Study for the Prevalence of Anti-MERS Coronavirus Antibodies in High- and Low-Risk Groups in Qatar
journal, February 2019
- Al Kahlout, Reham A.; Nasrallah, Gheyath K.; Farag, Elmoubasher A.
- Journal of Immunology Research, Vol. 2019
Stalking new vaccines: Methods that target the stems of viral proteins could put universal vaccines within reach
journal, November 2017
- Arnold, Carrie
- Nature Medicine, Vol. 23, Issue 11
Alternative conformations of a major antigenic site on RSV F
journal, July 2019
- Jones, Harrison G.; Battles, Michael B.; Lin, Chun-Chi
- PLOS Pathogens, Vol. 15, Issue 7
Recent Advances in the Vaccine Development Against Middle East Respiratory Syndrome-Coronavirus
journal, August 2019
- Yong, Chean Yeah; Ong, Hui Kian; Yeap, Swee Keong
- Frontiers in Microbiology, Vol. 10
Moving from Empirical to Rational Vaccine Design in the ‘Omics’ Era
journal, August 2019
- Sharma, Mansi; Krammer, Florian; García-Sastre, Adolfo
- Vaccines, Vol. 7, Issue 3
Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation
journal, February 2020
- Wrapp, Daniel; Wang, Nianshuang; Corbett, Kizzmekia S.
- Science, Vol. 367, Issue 6483
CD8+ T Cells Responding to the Middle East Respiratory Syndrome Coronavirus Nucleocapsid Protein Delivered by Vaccinia Virus MVA in Mice
journal, December 2018
- Veit, Svenja; Jany, Sylvia; Fux, Robert
- Viruses, Vol. 10, Issue 12
Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses
journal, February 2020
- Wang, Ning; Shang, Jian; Jiang, Shibo
- Frontiers in Microbiology, Vol. 11
Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion
journal, October 2017
- Walls, Alexandra C.; Tortorici, M. Alejandra; Snijder, Joost
- Proceedings of the National Academy of Sciences, Vol. 114, Issue 42
Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein
journal, December 2020
- Walls, Alexandra C.; Park, Young-Jun; Tortorici, M. Alejandra
- Cell, Vol. 183, Issue 6
Cryo-EM structure of infectious bronchitis coronavirus spike protein reveals structural and functional evolution of coronavirus spike proteins
journal, April 2018
- Shang, Jian; Zheng, Yuan; Yang, Yang
- PLOS Pathogens, Vol. 14, Issue 4
The 3.1-Angstrom Cryo-electron Microscopy Structure of the Porcine Epidemic Diarrhea Virus Spike Protein in the Prefusion Conformation
journal, September 2019
- Wrapp, Daniel; McLellan, Jason S.
- Journal of Virology, Vol. 93, Issue 23
Stabilized coronavirus spikes are resistant to conformational changes induced by receptor recognition or proteolysis
journal, October 2018
- Kirchdoerfer, Robert N.; Wang, Nianshuang; Pallesen, Jesper
- Scientific Reports, Vol. 8, Issue 1
Antibodies and vaccines against Middle East respiratory syndrome coronavirus
journal, January 2019
- Xu, Jiuyang; Jia, Wenxu; Wang, Pengfei
- Emerging Microbes & Infections, Vol. 8, Issue 1
Cryo-EM Studies of Virus-Antibody Immune Complexes
journal, January 2020
- Li, Na; Li, Zhiqiang; Fu, Yan
- Virologica Sinica, Vol. 35, Issue 1
Exploitation of glycosylation in enveloped virus pathobiology
journal, October 2019
- Watanabe, Yasunori; Bowden, Thomas A.; Wilson, Ian A.
- Biochimica et Biophysica Acta (BBA) - General Subjects, Vol. 1863, Issue 10
Common Features of Enveloped Viruses and Implications for Immunogen Design for Next-Generation Vaccines
journal, March 2018
- Rey, Felix A.; Lok, Shee-Mei
- Cell, Vol. 172, Issue 6
Structural Definition of a Unique Neutralization Epitope on the Receptor-Binding Domain of MERS-CoV Spike Glycoprotein
journal, July 2018
- Zhang, Senyan; Zhou, Panpan; Wang, Pengfei
- Cell Reports, Vol. 24, Issue 2
The Chimpanzee SIV Envelope Trimer: Structure and Deployment as an HIV Vaccine Template
journal, May 2019
- Andrabi, Raiees; Pallesen, Jesper; Allen, Joel D.
- Cell Reports, Vol. 27, Issue 8
Structural Definition of a Neutralization-Sensitive Epitope on the MERS-CoV S1-NTD
journal, September 2019
- Wang, Nianshuang; Rosen, Osnat; Wang, Lingshu
- Cell Reports, Vol. 28, Issue 13
Structure-Based Design of Prefusion-Stabilized Filovirus Glycoprotein Trimers
journal, March 2020
- Rutten, Lucy; Gilman, Morgan S. A.; Blokland, Sven
- Cell Reports, Vol. 30, Issue 13
Molecular Characteristics, Functions, and Related Pathogenicity of MERS-CoV Proteins
journal, October 2019
- Li, Yan-Hua; Hu, Chen-Yu; Wu, Nan-Ping
- Engineering, Vol. 5, Issue 5
X-ray Structures of the Post-fusion 6-Helix Bundle of the Human Syncytins and their Functional Implications
journal, December 2019
- Ruigrok, Katinka; Vaney, Marie-Christine; Buchrieser, Julian
- Journal of Molecular Biology, Vol. 431, Issue 24
A high-throughput inhibition assay to study MERS-CoV antibody interactions using image cytometry
journal, March 2019
- Rosen, Osnat; Chan, Leo Li-Ying; Abiona, Olubukola M.
- Journal of Virological Methods, Vol. 265
Detection of MERS-CoV antigen on formalin-fixed paraffin-embedded nasal tissue of alpacas by immunohistochemistry using human monoclonal antibodies directed against different epitopes of the spike protein
journal, December 2019
- Haverkamp, Ann-Kathrin; Bosch, Berend J.; Spitzbarth, Ingo
- Veterinary Immunology and Immunopathology, Vol. 218
Characterization of novel monoclonal antibodies against MERS-coronavirus spike protein
journal, March 2020
- Goo, Junghyun; Jeong, Yuji; Park, Young-Shin
- Virus Research, Vol. 278
Global site-specific analysis of glycoprotein N-glycan processing
journal, May 2018
- Cao, Liwei; Diedrich, Jolene K.; Ma, Yuanhui
- Nature Protocols, Vol. 13, Issue 6
Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein
journal, July 2019
- Zhou, Haixia; Chen, Yingzhu; Zhang, Shuyuan
- Nature Communications, Vol. 10, Issue 1
Structural basis for human coronavirus attachment to sialic acid receptors
journal, June 2019
- Tortorici, M. Alejandra; Walls, Alexandra C.; Lang, Yifei
- Nature Structural & Molecular Biology, Vol. 26, Issue 6
Structures of MERS-CoV spike glycoprotein in complex with sialoside attachment receptors
journal, December 2019
- Park, Young-Jun; Walls, Alexandra C.; Wang, Zhaoqian
- Nature Structural & Molecular Biology, Vol. 26, Issue 12
Stabilized coronavirus spikes are resistant to conformational changes induced by receptor recognition or proteolysis
journal, October 2018
- Kirchdoerfer, Robert N.; Wang, Nianshuang; Pallesen, Jesper
- Scientific Reports, Vol. 8, Issue 1
Antibodies and vaccines against Middle East respiratory syndrome coronavirus
journal, January 2019
- Xu, Jiuyang; Jia, Wenxu; Wang, Pengfei
- Emerging Microbes & Infections, Vol. 8, Issue 1
Structural basis of SARS-CoV-2 spike protein induced by ACE2
journal, August 2020
- Meirson, Tomer; Bomze, David; Markel, Gal
- Bioinformatics, Vol. 37, Issue 7
New Vaccine Design and Delivery Technologies
journal, April 2019
- Kanekiyo, Masaru; Ellis, Daniel; King, Neil P.
- The Journal of Infectious Diseases, Vol. 219, Issue Supplement_1
Comparative Serological Study for the Prevalence of Anti-MERS Coronavirus Antibodies in High- and Low-Risk Groups in Qatar
journal, February 2019
- Al Kahlout, Reham A.; Nasrallah, Gheyath K.; Farag, Elmoubasher A.
- Journal of Immunology Research, Vol. 2019
Stabilizing HIV-1 envelope glycoprotein trimers to induce neutralizing antibodies
journal, September 2018
- Torrents de la Peña, Alba; Sanders, Rogier W.
- Retrovirology, Vol. 15, Issue 1
Superior immune responses induced by intranasal immunization with recombinant adenovirus-based vaccine expressing full-length Spike protein of Middle East respiratory syndrome coronavirus
journal, July 2019
- Kim, Myung Hee; Kim, Hyun Jik; Chang, Jun
- PLOS ONE, Vol. 14, Issue 7
Cryo-EM structure of infectious bronchitis coronavirus spike protein reveals structural and functional evolution of coronavirus spike proteins
journal, April 2018
- Shang, Jian; Zheng, Yuan; Yang, Yang
- PLOS Pathogens, Vol. 14, Issue 4
Alternative conformations of a major antigenic site on RSV F
journal, July 2019
- Jones, Harrison G.; Battles, Michael B.; Lin, Chun-Chi
- PLOS Pathogens, Vol. 15, Issue 7
Chimeric
Pneumoviridae
fusion proteins as immunogens to induce cross‐neutralizing antibody responses
journal, December 2017
- Olmedillas, Eduardo; Cano, Olga; Martínez, Isidoro
- EMBO Molecular Medicine, Vol. 10, Issue 2
Recent Aspects on the Pathogenesis Mechanism, Animal Models and Novel Therapeutic Interventions for Middle East Respiratory Syndrome Coronavirus Infections
journal, March 2019
- Skariyachan, Sinosh; Challapilli, Sneha Basavaraj; Packirisamy, Swathi
- Frontiers in Microbiology, Vol. 10
Recent Advances in the Vaccine Development Against Middle East Respiratory Syndrome-Coronavirus
journal, August 2019
- Yong, Chean Yeah; Ong, Hui Kian; Yeap, Swee Keong
- Frontiers in Microbiology, Vol. 10
Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses
journal, February 2020
- Wang, Ning; Shang, Jian; Jiang, Shibo
- Frontiers in Microbiology, Vol. 11
Advances in MERS-CoV Vaccines and Therapeutics Based on the Receptor-Binding Domain
journal, January 2019
- Zhou, Yusen; Yang, Yang; Huang, Jingwei
- Viruses, Vol. 11, Issue 1
Middle East Respiratory Syndrome Vaccine Candidates: Cautious Optimism
journal, January 2019
- Schindewolf, Craig; Menachery, Vineet
- Viruses, Vol. 11, Issue 1
Moving from Empirical to Rational Vaccine Design in the ‘Omics’ Era
journal, August 2019
- Sharma, Mansi; Krammer, Florian; García-Sastre, Adolfo
- Vaccines, Vol. 7, Issue 3
Exploring the Regulatory Function of the N-terminal Domain of SARS-CoV-2 Spike Protein Through Molecular Dynamics Simulation
preprint, January 2021
- Li, Yao; Wang, Tong; Zhang, Juanrong
- arXiv