SARS-CoV-2 Spike glycoprotein | SARS-CoV-2 proteins | IUPHAR/BPS Guide to PHARMACOLOGY

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SARS-CoV-2 Spike glycoprotein

Target not currently curated in GtoImmuPdb

Target id: 3114

Nomenclature: SARS-CoV-2 Spike glycoprotein

Family: SARS-CoV-2 proteins

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
SARS-CoV-2 - 1273 S
Previous and Unofficial Names
spike protein
Database Links
Entrez Gene
Selected 3D Structures
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:  1
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:  4
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:  5
General Comments
The SARS-CoV-2 S protein is key to its infection of human cells. It 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 [4]. 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 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 [3].

The monoclonal antibody CR3022 was designed to neutralise SARS-CoV [2]. 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 [5]. X-ray analysis of SARS-CoV-2 spike/CR3003 crystals shows that the antibody targets a highly conserved epitope in S that is distal from the receptor (ACE2)-binding site. The antobody can only gian access to the epitope when at least two RBD on the trimeric S protein are in the "up" conformation.


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1. 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, [Epub ahead of print]. [PMID:32225176]

2. 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]

3. 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]

4. 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]

5. 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]

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