Spike glycoprotein of SARS-CoV-2 binds ACE2 on host cell

Stable Identifier
Reaction [binding]
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
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SARS-CoV-2 spike protein trimer (S3), as a component of the S3:M:E:encapsidated SARS coronavirus-2 genomic RNA: 7a:O-glycosyl 3a tetramer complex, binds to glycosylated angiotensin converting enzyme 2 (ACE2) associated with the human host cell plasma membrane (Zhang et al, 2020; Raghuvamsi et al, 2021; reviewed by Jackson et al, 2022). Glycosylation of both molecules is the most important factor in their interaction (reviewed by Reis et al, 2021; Shajahan et al, 2021; Gong et al, 2021). Spike binding to ACE2 also requires the presence of heparan sulfate (HS) on the cell surface, consistent with the formation of a ternary complex between S, ACE2, and heparan sulfate proteoglycans (HSPGs) (Kim et al, 2020; Zhang et al, 2020; Clausen et al, 2021; Liu et al, 2021; Yue et al, 2021; Bermejo-Jambrina et al, 2021).

In SARS-CoV-1 structural studies of the interaction between human ACE2 protein and the receptor-binding domain of S3 protein have identified key amino acid residues in both proteins responsible for their high-affinity interaction. These residues may be a key factor determining severity (and possibly human-to-human transmission) of SARS-CoV-1 (Li et al. 2003, 2005). The roles of S protein in viral binding to the host cell membrane and fusion of viral and host cell membranes and thus the central role of S protein in determining the host range and tissue tropisms of the virus are reviewed by Belouzard et al. (2012) and Jackson et al. (2022).
Literature References
PubMed ID Title Journal Year
34510494 Infection and transmission of SARS-CoV-2 depend on heparan sulfate proteoglycans

Geijtenbeek, TBH, Spaargaren, M, Bermejo-Jambrina, M, van Hamme, JL, van Gils, MJ, Brouwer, PJM, Helgers, LC, Vlaming, KE, van Nuenen, AC, Kaptein, TM, Kootstra, NA, Nijmeijer, BM, de Bree, GJ, Sanders, RW, Eder, J

EMBO J 2021
32653452 Characterization of heparin and severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) spike glycoprotein binding interactions

Linhardt, RJ, Zhang, F, Woods, RJ, Fu, L, Sood, A, Kim, SY, Jin, W, Montgomery, DW, Fuster, MM, Grant, OC, Dordick, JS

Antiviral Res 2020
33298900 Heparan sulfate assists SARS-CoV-2 in cell entry and can be targeted by approved drugs in vitro

Swaroop, M, Huang, W, Ye, Y, Shen, M, Hagen, N, Wang, AQ, Luo, Z, Wang, L, Pradhan, M, Zheng, W, Xu, X, Lee, J, Chen, CZ, Xu, M, Zhang, Q, Chen, L, Xu, Y

Cell Discov 2020
34782609 The glycosylation in SARS-CoV-2 and its receptor ACE2

Qin, S, Gong, Y, Tian, Z, Dai, L

Signal Transduct Target Ther 2021
34611326 Mechanisms of SARS-CoV-2 entry into cells

Jackson, CB, Farzan, M, Choe, H, Chen, B

Nat Rev Mol Cell Biol 2022
22816037 Mechanisms of coronavirus cell entry mediated by the viral spike protein

Licitra, BN, Belouzard, S, Millet, JK, Whittaker, GR

Viruses 2012
32125455 Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target

Li, Y, Penninger, JM, Zhang, H, Slutsky, AS, Zhong, N

Intensive Care Med 2020
34235568 Glycosylation of SARS-CoV-2: structural and functional insights

Shajahan, A, Pepi, LE, Heiss, C, Azadi, P, Rouhani, DS

Anal Bioanal Chem 2021
34235261 Heparan Sulfate Proteoglycans as Attachment Factor for SARS-CoV-2

Bouwman, KM, Tompkins, SM, Boons, GJ, de Vries, RP, Liu, L, Chopra, P, Wolfert, MA, Li, X

ACS Cent Sci 2021
32970989 SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2

Majowicz, SA, Narayanan, A, Ward, AB, Kwong, EM, Gordts, PLSM, Corbett, KD, Thacker, BE, Glass, CA, Esko, JD, Chanda, SK, Perrett, HR, Laubach, L, McVicar, RN, Bartels, PL, Feldman, J, Jose, J, Porell, RN, Torres, JL, Martino, C, Schmidt, AG, Godula, K, Hauser, BM, Carlin, AF, Golden, GJ, Caradonna, TM, Yin, X, Yang, Z, Garretson, AF, Pihl, J, Sandoval, DR, Kellman, BP, Pu, Y, Painter, CD, Spliid, CB, Clausen, TM, Leibel, SL

Cell 2020
34023935 Glycosylation is a key in SARS-CoV-2 infection

Reis, CA, Blanchard, V, Tauber, R

J Mol Med (Berl) 2021
34179075 Heparan Sulfate Facilitates Spike Protein-Mediated SARS-CoV-2 Host Cell Invasion and Contributes to Increased Infection of SARS-CoV-2 G614 Mutant and in Lung Cancer

Qiu, H, Song, X, Linhardt, RJ, Yue, J, Zhang, F, Jin, W, Wang, L, Azadi, P, Faulkner, J, Yang, H, Teng, M

Front Mol Biosci 2021
33554856 SARS-CoV-2 S protein:ACE2 interaction reveals novel allosteric targets

Bond, PJ, Hwa, WY, Purushotorman, K, Lescar, J, Raghuvamsi, PV, MacAry, PA, Anand, GS, Qian, X, Samsudin, F, Kozma, MM, Yue, G, Tulsian, NK

Elife 2021
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Name Identifier Synonyms
COVID-19 DOID:0080600 2019 Novel Coronavirus (2019-nCoV), Wuhan seafood market pneumonia virus infection, 2019-nCoV infection, Wuhan coronavirus infection
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