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. 2021 Jun 30;66(12):1205-1214.
doi: 10.1016/j.scib.2021.01.010. Epub 2021 Jan 19.

Binding of the SARS-CoV-2 spike protein to glycans

Wei Hao  1 , Bo Ma  2 , Ziheng Li  1 , Xiaoyu Wang  2 , Xiaopan Gao  1 , Yaohao Li  2   3 , Bo Qin  1 , Shiying Shang  4 , Sheng Cui  1 , Zhongping Tan  2
Affiliations

Binding of the SARS-CoV-2 spike protein to glycans

Wei Hao et al. Sci Bull (Beijing). .

Abstract

The pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a high number of deaths in the world. To combat it, it is necessary to develop a better understanding of how the virus infects host cells. Infection normally starts with the attachment of the virus to cell-surface glycans like heparan sulfate (HS) and sialic acid-containing glycolipids/glycoproteins. In this study, we examined and compared the binding of the subunits and spike (S) proteins of SARS-CoV-2, SARS-CoV, and Middle East respiratory disease (MERS)-CoV to these glycans. Our results revealed that the S proteins and subunits can bind to HS in a sulfation-dependent manner and no binding with sialic acid residues was detected. Overall, this work suggests that HS binding may be a general mechanism for the attachment of these coronaviruses to host cells, and supports the potential importance of HS in infection and in the development of antiviral agents against these viruses.

Keywords: Glycan microarray; Heparan sulfate; SARS-CoV-2 S protein; Sialic acid; Sulfation; Surface plasmon resonance.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

None
Graphical abstract
Fig. 1
Fig. 1
A possible mechanism for SARS-CoV-2 entry and infection. At the early stage of the infection process, SARS-CoV-2 may first interact with the HSPGs on the surface of susceptible cells using the S protein protruding from the virus particle. This initial attachment may promote the subsequent binding of the virus to the high-affinity entry receptor ACE2. The transmembrane protease serine 2 (TMPRSS2) on host cell surface and other host cell proteases may assist in viral entry by cleaving the S protein at the S1/S2 and/or at the S2’ sites.
Fig. 2
Fig. 2
Schematic representation of CoV S proteins. The diagrams show the domain organization of the S proteins of SARS-CoV-2, SARS-CoV, and MERS-CoV. The sequences of the S1/S2 and S2’ cleavage sites are given on top of each diagram. The arrows indicate the cleave points.
Fig. 3
Fig. 3
The numbering and structures of the HS oligosaccharides on the microarray. Each HS chain is covalently attached to the microarray slide via the reducing end. The HS oligosaccharides can be roughly divided into five groups according to their differences in the monosaccharide compositions and sulfation patterns.
Fig. 4
Fig. 4
The binding of full-length CoV S proteins and their domains to HS microarrays. (a) SARS-CoV-2-RBD binding at the concentration of 2.5 μg/mL, (b) SARS-CoV-2-S1 at the concentration of 2 μg/mL, (c) SARS-CoV-2-S2 at the concentration of 2 μg/mL, (d) SARS-CoV-2-S at the concentration of 2 μg/mL, (e) SARS-CoV-2-trimer at the concentration of 2 μg/mL, (f) SARS-CoV-RBD at the concentration of 2 μg/mL, (g) SARS-CoV-S1 at the concentration of 2 μg/mL, (h) SARS-CoV-2-S at the concentration of 2 μg/mL, (i) MERS-CoV-RBD at the concentration of 4 μg/mL, (j) MERS-CoV-S1 at the concentration of 4 μg/mL, (k) MERS-CoV-S2 at the concentration of 2 μg/mL, (l) MERS-CoV-S at the concentration of 2 μg/mL. The fluorescence intensity was measured at an excitation wavelength of 532 nm. All error bars are standard deviation of more than three replicates.
Fig. 5
Fig. 5
SPR sensorgrams of the interactions between a commercially available porcine heparin and immobilized S proteins and their domains. Panels (a−l) show the binding of heparin to SARS-CoV-2-RBD, S1, S2, S, trimer, SARS-CoV-RBD, S1, S, and MERS-CoV-RBD, S1, S2, S, respectively. The name of each protein and its KD value are presented on top of the corresponding sensorgram. RU, resonance unit.
Fig. 6
Fig. 6
SPR sensorgrams of the interactions between fondaparinux and immobilized S proteins and their domains. Panels (a–l) are the binding of fondaparinux to SARS-CoV-2-RBD, S1, S2, S, trimer, SARS-CoV-RBD, S1, S, and MERS-CoV-RBD, S1, S2, S, respectively. The name and KD value of each protein are presented on top of the corresponding sensorgram. RU, resonance unit.
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