Host Cell Glycocalyx Remodeling Reveals SARS-CoV-2 Spike Protein Glycomic Binding Sites
Alvarez, Michael Russelle S
Lebrilla, Carlito B
JournalFrontiers in Molecular Biosciences
MetadataShow full item record
AbstractGlycans on the host cell membrane and viral proteins play critical roles in pathogenesis. Highly glycosylated epithelial cells represent the primary boundary separating embedded host tissues from pathogens within the respiratory and intestinal tracts. SARS-CoV-2, the causative agent for the COVID-19 pandemic, reaches into the respiratory tract. We found purified human milk oligosaccharides (HMOs) inhibited the viral binding on cells. Spike (S) protein receptor binding domain (RBD) binding to host cells were partly blocked by co-incubation with exogenous HMOs, most by 2-6-sialyl-lactose (6′SL), supporting the notion that HMOs can function as decoys in defense against SARS-Cov2. To investigate the effect of host cell glycocalyx on viral adherence, we metabolically modified and confirmed with glycomic methods the cell surface glycome to enrich specific N-glycan types including those containing sialic acids, fucose, mannose, and terminal galactose. Additionally, Immunofluorescence studies demonstrated that the S protein preferentially binds to terminal sialic acids with α-(2,6)-linkages. Furthermore, site-specific glycosylation of S protein RBD and its human receptor ACE2 were characterized using LC-MS/MS. We then performed molecular dynamics calculations on the interaction complex to further explore the interactive complex between ACE2 and the S protein. The results showed that hydrogen bonds mediated the interactions between ACE2 glycans and S protein with desialylated glycans forming significantly fewer hydrogen bonds. These results supported a mechanism where the virus binds initially to glycans on host cells preferring α-(2,6)-sialic acids and finds ACE2 and with the proper orientation infects the cell.
Rights/TermsCopyright © 2022 Sheng, Vinjamuri, Alvarez, Xie, McGrath, Chen, Barboza, Frieman and Lebrilla.
Spike Glycoprotein, Coronavirus
Host Microbial Interactions
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/18522
- Inhibition of SARS-CoV-2 viral entry upon blocking N- and O-glycan elaboration.
- Authors: Yang Q, Hughes TA, Kelkar A, Yu X, Cheng K, Park S, Huang WC, Lovell JF, Neelamegham S
- Issue date: 2020 Oct 26
- A Linkage-specific Sialic Acid Labeling Strategy Reveals Different Site-specific Glycosylation Patterns in SARS-CoV-2 Spike Protein Produced in CHO and HEK Cell Substrates.
- Authors: Wang Q, Wang Y, Yang S, Lin C, Aliyu L, Chen Y, Parsons L, Tian Y, Jia H, Pekosz A, Betenbaugh MJ, Cipollo JF
- Issue date: 2021
- Dual nature of human ACE2 glycosylation in binding to SARS-CoV-2 spike.
- Authors: Mehdipour AR, Hummer G
- Issue date: 2021 May 11
- Site-Specific Glycosylation Patterns of the SARS-CoV-2 Spike Protein Derived From Recombinant Protein and Viral WA1 and D614G Strains.
- Authors: Tian Y, Parsons LM, Jankowska E, Cipollo JF
- Issue date: 2021
- S494 O-glycosylation site on the SARS-CoV-2 RBD affects the virus affinity to ACE2 and its infectivity; a molecular dynamics study.
- Authors: Rahnama S, Azimzadeh Irani M, Amininasab M, Ejtehadi MR
- Issue date: 2021 Jul 26