Skip to content
naulon

No retraction, correction or concern found when last checked on Oct 29, 2026.

Distinct conformational states of SARS-CoV-2 spike protein

Yongfei Cai, Jun Zhang, Tianshu Xiao and 6 more

Science · 2020 · CC BY

doi:10.1126/science.abd4251

Abstract

A dynamic viral spike Efforts to protect human cells against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have focused on the trimeric spike (S) protein. Several structures have shown a stabilized ectodomain of the spike in its prefusion conformation. Cai et al. now provide insight into the structural changes in the S protein that result in the fusion of the viral and host cell membranes. They purified full-length S protein and determined cryo–electron microscopy structures of both the prefusion and postfusion conformations. These structures add to our understanding of S protein function and could inform vaccine design. Science , this issue p. 1586

References 57

  1. 1.

    de Wit E., van Doremalen N., Falzarano D., Munster V. J., SARS and MERS: Recent insights into emerging coronaviruses. Nat. Rev. Microbiol. 14, 523–534 (2016 ).

    Not in our library10.1038/nrmicro.2016.81

  2. 2.

    Zhong N. S., Zheng B. J., Li Y. M., Poon L. L. M., Xie Z. H., Chan K. H., Li P. H., Tan S. Y., Chang Q., Xie J. P., Liu X. Q., Xu J., Li D. X., Yuen K. Y., Peiris J. S. M., Guan Y., Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People’s Republic of China, in February, 2003. Lancet 362, 1353–1358 (2003 ).

    Not in our library10.1016/s0140-6736(03)14630-2

  3. 3.

    Hijawi B., Abdallat M., Sayaydeh A., Alqasrawi S., Haddadin A., Jaarour N., Alsheikh S., Alsanouri T., Novel coronavirus infections in Jordan, April 2012: Epidemiological findings from a retrospective investigation. East. Mediterr. Health J. 19, S12–S18 (2013 ).

    Not in our library10.26719/2013.19.supp1.s12

  4. 4.

    Corman V. M., Muth D., Niemeyer D., Drosten C., Hosts and sources of endemic human coronaviruses. Adv. Virus Res. 100, 163–188 (2018 ).

    Not in our library10.1016/bs.aivir.2018.01.001

  5. 5.

    Guan Y., Zheng B. J., He Y. Q., Liu X. L., Zhuang Z. X., Cheung C. L., Luo S. W., Li P. H., Zhang L. J., Guan Y. J., Butt K. M., Wong K. L., Chan K. W., Lim W., Shortridge K. F., Yuen K. Y., Peiris J. S., Poon L. L., Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China. Science 302, 276–278 (2003 ).

    Not in our library10.1126/science.1087139

  6. 6.
  7. 7.
  8. 8.
    Bats and Coronaviruses · 2019
    No notice
  9. 9.
  10. 10.
  11. 11.

    Rand R. P., Parsegian V. A., Physical force considerations in model and biological membranes. Can. J. Biochem. Cell Biol. 62, 752–759 (1984 ).

    Not in our library10.1139/o84-097

  12. 12.

    Parsegian V. A., Fuller N., Rand R. P., Measured work of deformation and repulsion of lecithin bilayers. Proc. Natl. Acad. Sci. U.S.A. 76, 2750–2754 (1979 ).

    Not in our library10.1073/pnas.76.6.2750

  13. 13.

    Harrison S. C., Viral membrane fusion. Virology 479-480, 498–507 (2015 ).

    Not in our library10.1016/j.virol.2015.03.043

  14. 14.

    Kielian M., Mechanisms of virus membrane fusion proteins. Annu. Rev. Virol. 1, 171–189 (2014 ).

    Not in our library10.1146/annurev-virology-031413-085521

  15. 15.

    Weissenhorn W., Dessen A., Calder L. J., Harrison S. C., Skehel J. J., Wiley D. C., Structural basis for membrane fusion by enveloped viruses. Mol. Membr. Biol. 16, 3–9 (1999 ).

    Not in our library10.1080/096876899294706

  16. 16.

    Du L., He Y., Zhou Y., Liu S., Zheng B.-J., Jiang S., The spike protein of SARS-CoV—A target for vaccine and therapeutic development. Nat. Rev. Microbiol. 7, 226–236 (2009 ).

    Not in our library10.1038/nrmicro2090

  17. 17.

    Bosch B. J., van der Zee R., de Haan C. A., Rottier P. J., The coronavirus spike protein is a class I virus fusion protein: Structural and functional characterization of the fusion core complex. J. Virol. 77, 8801–8811 (2003 ).

    Not in our library10.1128/jvi.77.16.8801-8811.2003

  18. 18.

    Hoffmann M., Kleine-Weber H., Schroeder S., Krüger N., Herrler T., Erichsen S., Schiergens T. S., Herrler G., Wu N.-H., Nitsche A., Müller M. A., Drosten C., Pöhlmann S., SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181, 271–280.e8 (2020 ).

    Not in our library10.1016/j.cell.2020.02.052

  19. 19.

    Millet J. K., Whittaker G. R., Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein. Proc. Natl. Acad. Sci. U.S.A. 111, 15214–15219 (2014 ).

    Not in our library10.1073/pnas.1407087111

  20. 20.

    Tortorici M. A., Veesler D., Structural insights into coronavirus entry. Adv. Virus Res. 105, 93–116 (2019 ).

    Not in our library10.1016/bs.aivir.2019.08.002

  21. 21.
  22. 22.

    Wrapp D., Wang N., Corbett K. S., Goldsmith J. A., Hsieh C.-L., Abiona O., Graham B. S., McLellan J. S., Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 367, 1260–1263 (2020 ).

    Not in our library10.1126/science.abb2507

  23. 23.

    Walls A. C., Park Y.-J., Tortorici M. A., Wall A., McGuire A. T., Veesler D., Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 181, 281–292.e6 (2020 ).

    Not in our library10.1016/j.cell.2020.02.058

  24. 24.

    R. Henderson, R. Henderson, R. J. Edwards, K. Mansouri, K. Janowska, V. Stalls, S. Gobeil, M. Kopp, A. Hsu, M. Borgnia, R. Parks, B. F. Haynes, P. Acharya, Controlling the SARS-CoV-2 spike glycoprotein conformation. bioRxiv 2020.05.18.102087 [Preprint]. 18 May 2020;.

    Not in our library10.1101/2020.05.18.102087

  25. 25.

    Lan J., Ge J., Yu J., Shan S., Zhou H., Fan S., Zhang Q., Shi X., Wang Q., Zhang L., Wang X., Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature 581, 215–220 (2020 ).

    Not in our library10.1038/s41586-020-2180-5

  26. 26.
  27. 27.

    Shang J., Ye G., Shi K., Wan Y., Luo C., Aihara H., Geng Q., Auerbach A., Li F., Structural basis of receptor recognition by SARS-CoV-2. Nature 581, 221–224 (2020 ).

    Not in our library10.1038/s41586-020-2179-y

  28. 28.

    Wang Q., Zhang Y., Wu L., Niu S., Song C., Zhang Z., Lu G., Qiao C., Hu Y., Yuen K.-Y., Wang Q., Zhou H., Yan J., Qi J., Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell 181, 894–904.e9 (2020 ).

    Not in our library10.1016/j.cell.2020.03.045

  29. 29.

    Walls A. C., Tortorici M. A., Snijder J., Xiong X., Bosch B.-J., Rey F. A., Veesler D., Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion. Proc. Natl. Acad. Sci. U.S.A. 114, 11157–11162 (2017 ).

    Not in our library10.1073/pnas.1708727114

  30. 30.
  31. 31.

    Schroth-Diez B., Ludwig K., Baljinnyam B., Kozerski C., Huang Q., Herrmann A., The role of the transmembrane and of the intraviral domain of glycoproteins in membrane fusion of enveloped viruses. Biosci. Rep. 20, 571–595 (2000 ).

    Not in our library10.1023/a:1010415122234

  32. 32.

    Bosch B. J., de Haan C. A., Smits S. L., Rottier P. J., Spike protein assembly into the coronavirion: Exploring the limits of its sequence requirements. Virology 334, 306–318 (2005 ).

    Not in our library10.1016/j.virol.2005.02.001

  33. 33.

    Lontok E., Corse E., Machamer C. E., Intracellular targeting signals contribute to localization of coronavirus spike proteins near the virus assembly site. J. Virol. 78, 5913–5922 (2004 ).

    Not in our library10.1128/jvi.78.11.5913-5922.2004

  34. 34.

    Petit C. M., Melancon J. M., Chouljenko V. N., Colgrove R., Farzan M., Knipe D. M., Kousoulas K. G., Genetic analysis of the SARS-coronavirus spike glycoprotein functional domains involved in cell-surface expression and cell-to-cell fusion. Virology 341, 215–230 (2005 ).

    Not in our library10.1016/j.virol.2005.06.046

  35. 35.

    Ye R., Montalto-Morrison C., Masters P. S., Genetic analysis of determinants for spike glycoprotein assembly into murine coronavirus virions: Distinct roles for charge-rich and cysteine-rich regions of the endodomain. J. Virol. 78, 9904–9917 (2004 ).

    Not in our library10.1128/jvi.78.18.9904-9917.2004

  36. 36.

    Hurtley S. M., Bole D. G., Hoover-Litty H., Helenius A., Copeland C. S., Interactions of misfolded influenza virus hemagglutinin with binding protein (BiP). J. Cell Biol. 108, 2117–2126 (1989 ).

    Not in our library10.1083/jcb.108.6.2117

  37. 37.
  38. 38.
  39. 39.
  40. 40.
  41. 41.

    Danieli T., Pelletier S. L., Henis Y. I., White J. M., Membrane fusion mediated by the influenza virus hemagglutinin requires the concerted action of at least three hemagglutinin trimers. J. Cell Biol. 133, 559–569 (1996 ).

    Not in our library10.1083/jcb.133.3.559

  42. 42.

    C. Liu, Y. Yang, Y. Gao, C. Shen, B. Ju, C. Liu, X. Tang, J. Wei, X. Ma, W. Liu, S. Xu, Y. Liu, J. Yuan, J. Wu, Z. Liu, Z. Zhang, P. Wang, L. Liu, Viral architecture of SARS-CoV-2 with post-fusion spike revealed by cryo-EM. bioRxiv 2020.03.02.972927 [Preprint]. 5 March 2020;.

    Not in our library10.1101/2020.03.02.972927

  43. 43.
  44. 44.

    F. Wu, A. Wang, M. Liu, Q. Wang, J. Chen, S. Xia, Y. Ling, Y. Zhang, J. Xun, L. Lu, S. Jiang, H. Lu, Y. Wen, J. Huang, Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications. medRxiv 2020.03.30.20047365 [Preprint]. 20 April 2020;.

    Not in our library10.1101/2020.03.30.20047365

  45. 45.

    McLellan J. S., Chen M., Joyce M. G., Sastry M., Stewart-Jones G. B. E., Yang Y., Zhang B., Chen L., Srivatsan S., Zheng A., Zhou T., Graepel K. W., Kumar A., Moin S., Boyington J. C., Chuang G.-Y., Soto C., Baxa U., Bakker A. Q., Spits H., Beaumont T., Zheng Z., Xia N., Ko S.-Y., Todd J.-P., Rao S., Graham B. S., Kwong P. D., Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus. Science 342, 592–598 (2013 ).

    Not in our library10.1126/science.1243283

  46. 46.

    Frey G., Chen J., Rits-Volloch S., Freeman M. M., Zolla-Pazner S., Chen B., Distinct conformational states of HIV-1 gp41 are recognized by neutralizing and non-neutralizing antibodies. Nat. Struct. Mol. Biol. 17, 1486–1491 (2010 ).

    Not in our library10.1038/nsmb.1950

  47. 47.

    Skehel J. J., Wiley D. C., Receptor binding and membrane fusion in virus entry: The influenza hemagglutinin. Annu. Rev. Biochem. 69, 531–569 (2000 ).

    Not in our library10.1146/annurev.biochem.69.1.531

  48. 48.

    Frey G., Peng H., Rits-Volloch S., Morelli M., Cheng Y., Chen B., A fusion-intermediate state of HIV-1 gp41 targeted by broadly neutralizing antibodies. Proc. Natl. Acad. Sci. U.S.A. 105, 3739–3744 (2008 ).

    Not in our library10.1073/pnas.0800255105

  49. 49.

    Kovacs J. M., Nkolola J. P., Peng H., Cheung A., Perry J., Miller C. A., Seaman M. S., Barouch D. H., Chen B., HIV-1 envelope trimer elicits more potent neutralizing antibody responses than monomeric gp120. Proc. Natl. Acad. Sci. U.S.A. 109, 12111–12116 (2012 ).

    Not in our library10.1073/pnas.1204533109

  50. 50.

    Chen J., Kovacs J. M., Peng H., Rits-Volloch S., Lu J., Park D., Zablowsky E., Seaman M. S., Chen B., Effect of the cytoplasmic domain on antigenic characteristics of HIV-1 envelope glycoprotein. Science 349, 191–195 (2015 ).

    Not in our library10.1126/science.aaa9804

  51. 51.

    Zheng S. Q., Palovcak E., Armache J.-P., Verba K. A., Cheng Y., Agard D. A., MotionCor2: Anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331–332 (2017 ).

    Not in our library10.1038/nmeth.4193

  52. 52.

    Rohou A., Grigorieff N., CTFFIND4: Fast and accurate defocus estimation from electron micrographs. J. Struct. Biol. 192, 216–221 (2015 ).

    Not in our library10.1016/j.jsb.2015.08.008

  53. 53.
  54. 54.

    Pettersen E. F., Goddard T. D., Huang C. C., Couch G. S., Greenblatt D. M., Meng E. C., Ferrin T. E., UCSF Chimera—A visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004 ).

    Not in our library10.1002/jcc.20084

  55. 55.
  56. 56.
  57. 57.

Cited by papers we hold 41

and 21 more

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.