Site-specific analysis of the SARS-CoV-2 glycan shield

Yasunori Watanabe; Joel D. Allen; Daniel Wrapp; Jason S. McLellan; Max Crispin

In addition to oligomannose-type glycans, the processing of complex-type glycans is an important consideration in immunogen engineering. Across the 22 N-linked glycosylation sites, 16% of the glycans contain at least one sialic acid residue and 48% are fucosylated (Figure 4) . These data suggest high levels of fucosylation but low levels of sialylation, considering complex and hybrid type glycans make up 69% of the total glycans of SARS-CoV-2. Understanding the distribution of glycan modifications across the viral spike illustrates the differential susceptibility to different processing enzymes while the absolute levels can be heavily influenced by the cellular expression system utilized. We have previously demonstrated for HIV-1 Env glycosylation that the processing of complex-type glycans is driven by the producer cell but that the levels of oligomannose-type glycans were largely independent of the expression system and is much more closely related to the protein structure and glycan density 38 .