Site-specific Analysis of the SARS-CoV-2 Glycan Shield

The emergence of the betacoronavirus, SARS-CoV-2 that causes COVID-19, represents a significant threat to global human health. Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, that mediates cell entry and membrane fusion. SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in immune evasion and occluding immunogenic protein epitopes. Here, using a site-specific mass spectrometric approach, the authors reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen. This analysis enables mapping of the glycan-processing states across the trimeric viral spike.

Copyright: Watanabe et al., bioRxiv, 26 03 2020

The modelling of experimentally observed glycosylation site compositions is illustrated on the prefusion structure of trimeric SARS-CoV-2 S glycoprotein (PDB ID 6VSB)18, with one RBD in the “up” conformation and the other two RBDs in the “down” conformation. The glycans are colored according to oligomannose content as defined by the key. ACE2 receptor binding sites are highlighted in light blue. The S1 and S2 subunits are rendered with translucent surface representation, colored light and dark grey, respectively. Note that the flexible loops on which N74 and N149 glycan sites reside are represented as dashed lines with glycan sites on the loops mapped at approximate regions.

The authors show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.