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

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

As obligate parasites, many viruses exploit host-cell machinery to glycosylate their own proteins. Numerous viral envelope proteins, including HIV-1 envelope (Env), influenza hemagglutinin (HA) and Lassa virus glycoprotein complex (GPC), possess genetically encoded N-linked glycan sequons (N-X-S/T motifs, where X is any amino acid except proline). Viral glycosylation has wide-ranging roles in viral pathobiology, including mediating protein folding and stability, and shaping viral tropism. The genetically encoded sequons can be under significant selective pressure as a mechanism for immune evasion by shielding specific epitopes from antibody neutralization. However, we note the currently reported low mutation rate of SARS-CoV-2, and as yet that there have been no observed mutations to N-linked glycosylation sites 4 . Surfaces with an unusually high density of glycans can also enable immune recognition [5] [6] [7] . The role of glycosylation in immune evasion by camouflaging immunogenic protein epitopes has been well studied for other coronaviruses 4,8,9 . As the principal antigen presented on the surface of SARS-CoV-2 virions, the S protein is a key target in vaccine design efforts. It is apparent that the viral spike will be targeted by the full assortment of vaccine strategies from nucleic-acid based approaches 10 , whereby the viral protein is expressed in vivo, to recombinant strategies whereby viral glycoproteins are delivered with appropriate adjuvants. Such strategies aim to elicit neutralizing adaptive immunity with an emphasis on achieving an antibody response at the sites of viral entry.