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

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

It is interesting to note the absence of a specific glycan cluster that is responsible for the presence of the oligomannose-type glycans but rather there is a dispersion of these glycans across both the S1 and S2 subunits. This is in significant contrast to other viral glycoproteins, for example the density of glycans clusters in HIV have even enabled structural classification of their different modes of interaction 36 . In SARS-CoV-2 the oligomannose-type structures are probably protected, to some extent, by the protein component, as exemplified by the N234 glycan which is partially sandwiched between the N-terminal and receptor-binding domains (Figure 3) . We characterized the N-linked glycans on extended loop structures that were not resolved in the cryo-EM maps 18 (N74 and N149) . These were determined to be complex-type glycans, consistent with the inherent flexibility of these regions and resulting accessibility of these residues to glycan processing enzymes. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.26.010322 doi: bioRxiv preprint Fig. 1) . Oligomannose-type glycans comprise 32% of the total glycan pool, with hybrid-type and complex-type glycans comprising 7% and 62%, respectively (Sup. Fig. 1) . Despite the potential impact of different local protein structure on glycan processing, the overall glycosylation of SARS-CoV-2 is comparable with SARS-CoV-1 S protein and other coronavirus S proteins 4, 8, 9, 15 . We have previously reported that a recombinant SARS-CoV-1 S mimetic also contained 32% oligomannose-type glycans showing a remarkable conservation in glycan processing across these coronaviruses. Whilst the oligomannose-type glycan content is well above that observed on typical host glycoproteins, it is significantly lower than is found on other viral glycoproteins. For example, one of the most densely glycosylated viral spike proteins is HIV-1 Env, which contains ~60% oligomannose-type glycans 20, 37 . This suggests that SARS-CoV-2 S protein is less densely glycosylated and that the glycans form much less of a shield compared with other viral glycoproteins including HIV Env and LASV GPC, which may be beneficial for the elicitation of potent neutralizing antibodies.