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CoV Spike glycoprotein

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Target not currently curated in GtoImmuPdb

Target id: 3114

Nomenclature: CoV Spike glycoprotein

Family: Coronavirus (CoV) proteins

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
SARS-CoV-2 1 1273 Orf2 S Spike glycoprotein
SARS-CoV 1 1255 Orf2 S Spike glycoprotein
Previous and Unofficial Names Click here for help
spike protein
Database Links Click here for help
Entrez Gene
RefSeq Protein
UniProtKB
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of SARS-CoV-2 spike receptor-binding domain bound with ACE2
PDB Id:  6M0J
Resolution:  2.45Å
Species:  SARS-CoV-2
References:  8
Image of receptor 3D structure from RCSB PDB
Description:  The 2019-nCoV RBD/ACE2-B0AT1 complex
PDB Id:  6M17
Resolution:  2.9Å
Species:  SARS-CoV-2
References:  12
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of SARS-CoV-2 receptor binding domain in complex with human antibody CR3022.
PDB Id:  6W41
Resolution:  3.08Å
Species:  SARS-CoV-2
References:  13
Image of receptor 3D structure from RCSB PDB
Description:  SARS-CoV-2 spike in complex with LCB1 (2RBDs open)
PDB Id:  7JZL
Ligand:  LCB1
Resolution:  2.7Å
Species:  SARS-CoV-2
References:  2

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Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
CR3022 Peptide SARS-CoV-2 Binding 8.2 pKd 10
pKd 8.2 (Kd 6.3x10-9 M) [10]
mAb 4A8 Peptide SARS-CoV-2 Binding 7.0 pKd 4
pKd 7.0 (Kd 9.27x10-8 M) [4]
Description: Binding affinity to the S1 domain of Spike protein, by bio-layer interferometry.
casirivimab Peptide SARS-CoV-2 - 10.2 pIC50 5
pIC50 10.2 (IC50 6.9x10-11 M) [5]
Description: IC50 for ability of mAb to compete with spike protein for binding to hACE2.
imdevimab Peptide SARS-CoV-2 - 9.6 pIC50 5
pIC50 9.6 (IC50 2.3x10-10 M) [5]
Description: IC50 for ability of mAb to compete with spike protein for binding to hACE2.
bamlanivimab Peptide SARS-CoV-2 Binding - -
cilgavimab Peptide SARS-CoV-2 Binding - - 14
[14]
tixagevimab Peptide SARS-CoV-2 Binding - - 14
[14]
etesevimab Peptide SARS-CoV-2 Binding - -
regdanvimab Peptide SARS-CoV-2 Binding - -
sotrovimab Peptide SARS-CoV-2 Binding - -
Antibody Comments
CR3022 binds SARS-CoV-1 spike protein with a Kd of 19 nM, using Spike RBD as analyte in a bio-layer interferometry assay [6].
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
heparin Small molecule or natural product Approved drug SARS-CoV-2 Binding 10.1 pKd 7
pKd 10.1 (Kd 7.3x10-11 M) [7]
Description: Binding affinity of trimeric SARS-CoV-2 spike protein to immobilized heparin.
LCB1 Peptide SARS-CoV-2 Binding >9.0 pKd 2
pKd >9.0 (Kd <1x10-9 M) [2]
LCB3 Peptide SARS-CoV-2 Binding >9.0 pKd 2
pKd >9.0 (Kd <1x10-9 M) [2]
alunacedase alfa Peptide SARS-CoV-2 Binding - -
General Comments
Coronavirus (CoV) spike (S) proteins mediate viral entry by attaching to proteins on target host cells. The SARS coronaviruses exploit ACE2 as their primary entry point. Tor2 was isolated and identified as the prototype SARS-CoV during the extensive SARS outbreak in 2002-2003. Its S protein is highly adapted to bind human ACE2.
The SARS CoV S proteins are key to their infection of human cells. S forms trimeric complexes which bind primarily to ACE2 on the surface of host cells to mediate viral entry and to facilitate insertion of its RNA genome into the host cells [12]. Crystal structures of S in closed, open and prefusion configurations have been deposited with the RCSB Protein Data Bank. A structure of spike receptor-binding domain (RBD) bound to ACE2 is represented in PDB accession 6M0J. Experimental evidence suggests that the ACE2 binding domain of SARS-CoV-2 S protein binds to ACE2 more avidly than the homologous domain of SARS-CoV S [11].

The furin cleavage site in SARS-CoV-2's spike protein is necessary for efficient infection, and appears to be required for syncytium formation. Chemical furin inhibitors suppress SARS-CoV-2-induced syncytium and block viral entry and replication [3].

The experimental monoclonal antibody CR3022 was designed to neutralise SARS-CoV [9]. It was developed from an antibody isolated from plasma collected from a convalescent SARS patient. CR3022 was discovered to bind SARS-CoV S protein, including escape mutants. It also binds to the SARS-CoV-2 S protein [13]. X-ray analysis of SARS-CoV-2 spike/CR3022 crystals shows that the antibody targets a highly conserved epitope in S that is distal from the receptor (ACE2)-binding site. The antibody can only gain access to the epitope when at least two RBD on the trimeric S protein are in the "up" conformation. Other anti-spike mAbs are in clinical development. Examples include AbCellera/Eli Lilly's LY-CoV555 (LY3819253) which is in phase 3 (NCT04497987), LY-CoV016 (LY3832479) which is in phase 2 (in combination with LY-CoV555 NCT04427501) and Celltrion's CT-P59 that is in phase 1 (NCT04525079). Antibodies that target different components of the virus will potentially be useful as co-agents to anti-spike mAbs for SARS-CoV-2 therapy and/or prophylaxis. Regeneron have a mAb cocktail (REGN-COV2) [1,5] that is being included in the UK's RECOVERY trial.

References

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1. Baum A, Fulton BO, Wloga E, Copin R, Pascal KE, Russo V, Giordano S, Lanza K, Negron N, Ni M et al.. (2020) Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, 369 (6506): 1014-1018. [PMID:32540904]

2. Cao L, Goreshnik I, Coventry B, Case JB, Miller L, Kozodoy L, Chen RE, Carter L, Walls AC, Park YJ et al.. (2020) De novo design of picomolar SARS-CoV-2 miniprotein inhibitors. Science, [Epub ahead of print]. DOI: 10.1126/science.abd9909 [PMID:32907861]

3. Cheng Y-W, Chao T-L, Li C-L, Chen P-J, Chang S-Y, Yeh S-H. (2020) Furin Inhibitors Block SARS-CoV-2 Spike Protein Cleavage to Suppress Virus Production and Cytopathic Effects. Cell Reports, [Epub ahead of print]. DOI: 10.1016/j.celrep.2020.108254

4. Chi Y, Yan R, Zhang J, Zhang G, Zhang Y, Hao M, Zhang Z, Fan P, Dong Y, Yang Y et al.. (2020) A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2. Science,. DOI: 10.1126/science.abc6952

5. Hansen J, Baum A, Pascal KE, Russo V, Giordano S, Wloga E, Fulton BO, Yan Y, Koon K, Patel K et al.. (2020) Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science, 369 (6506): 1010-1014. [PMID:32540901]

6. Huo J, Zhao Y, Ren J, Zhou D, Duyvesteyn HME, Ginn HM, Carrique L, Malinauskas T, Ruza RR, Shah PNM et al.. (2020) Neutralisation of SARS-CoV-2 by destruction of the prefusion Spike. Cell Host and Microbe, In press. DOI: 10.1016/j.chom.2020.06.010

7. Kim SY, Jin W, Sood A, Montgomery DW, Grant OC, Fuster MM, Fu L, Dordick JS, Woods RJ, Zhang F et al.. (2020) Characterization of heparin and severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) spike glycoprotein binding interactions. Antiviral Res.,: 104873 [Epub ahead of print]. [PMID:32653452]

8. Lan J, Ge J, Yu J, Shan S, Zhou H, Fan S, Zhang Q, Shi X, Wang Q, Zhang L et al.. (2020) Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature, 581 (7807): 215-220. [PMID:32225176]

9. ter Meulen J, van den Brink EN, Poon LL, Marissen WE, Leung CS, Cox F, Cheung CY, Bakker AQ, Bogaards JA, van Deventer E et al.. (2006) Human monoclonal antibody combination against SARS coronavirus: synergy and coverage of escape mutants. PLoS Med., 3 (7): e237. [PMID:16796401]

10. Tian X, Li C, Huang A, Xia S, Lu S, Shi Z, Lu L, Jiang S, Yang Z, Wu Y et al.. (2020) Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody. Emerg Microbes Infect, 9 (1): 382-385. [PMID:32065055]

11. Wang Q, Zhang Y, Wu L, Niu S, Song C, Zhang Z, Lu G, Qiao C, Hu Y, Yuen KY et al.. (2020) Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2. Cell, 181 (4): 894-904.e9. [PMID:32275855]

12. Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. (2020) Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science, 367 (6485): 1444-1448. [PMID:32132184]

13. Yuan M, Wu NC, Zhu X, Lee CD, So RTY, Lv H, Mok CKP, Wilson IA. (2020) A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV. Science, 368 (6491): 630-633. [PMID:32245784]

14. Zost SJ, Gilchuk P, Case JB, Binshtein E, Chen RE, Nkolola JP, Schäfer A, Reidy JX, Trivette A, Nargi RS et al.. (2020) Potently neutralizing and protective human antibodies against SARS-CoV-2. Nature, 584 (7821): 443-449. [PMID:32668443]

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