Glycomics/Glycoproteomics

SARS-CoV-2 / HIV

Glycosylation of the SARS-CoV-2 spike (S) protein significantly influences viral infectivity by affecting conformational dynamics, receptor interactions, and host immune responses. Throughout the pandemic, several variants of concern (VOCs) emerged, with mutations in the S protein leading to increased transmissibility and immune evasion. Our comparative analysis of the site-specific glycosylation and overall glycomic profiles of the wild-type Wuhan-Hu-1 strain (WT) and five VOCs-Alpha, Beta, Gamma, Delta, and Omicron, reveals a high conservation of both N- and O-glycosylation sites among these variants, particularly within the receptor-binding domain (RBD). This conservation suggests a critical role for glycosylation in maintaining viral fitness and implies a correlation between glycosylation patterns and the enhanced infectivity and transmissibility observed in these VOCs.

Figure 1. Relative abundances of four most intense glycoforms at each site of WT and VOCs.
Figure 1. Relative abundances of four most intense glycoforms at each site of WT and VOCs.
Figure 2. HCD MS/MS spectrum of the peptide VNFTNR showing b and y fragmant ion series, which confirms the presence of N-glycosylation at N20 site.
Figure 2. HCD MS/MS spectrum of the peptide VNFTNR showing b and y fragmant ion series, which confirms the presence of N-glycosylation at N20 site.

References:

  1. Shajahan, A., Pepi, L.E., Kumar, B. et al. Site specific N- and O-glycosylation mapping of the spike proteins of SARS-CoV-2 variants of concern. Sci Rep 13, 10053 (2023). https://doi.org/10.1038/s41598-023-33088-0.
  2. Pepi, L.E., Shajahan, A., Gleinich, A., Heiss C., Azadi, P. in Glycoprotein Analysis, ed. W. B. Struwe, Royal Society of Chemistry, 2024, vol. 15, ch. 1, pp. 1-28.