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Site-Specific Steric Control of SARS-CoV-2 Spike Glycosylation

Journal Type:  Journal Paper
Journal:  Biochemistry. 2021 Jul 13;60(27):2153-2169. doi: 10.1021/acs.biochem.1c00279. Epub 2021 Jul 2.
Pubmed:  34213308
Impact Factor:  2.952
Date of Acceptance:   18 Oct 2021

A central tenet in the design of vaccines is the display of native-like antigens in the elicitation of protective immunity. The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity among the many different vaccine candidates under investigation. Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against S protein from infectious virus, cultured in Vero cells. We find patterns that are conserved across all samples, and this can be associated with site-specific stalling of glycan maturation that acts as a highly sensitive reporter of protein structure. Molecular dynamics simulations of a fully glycosylated spike support a model of steric restrictions that shape enzymatic processing of the glycans. These results suggest that recombinant spike-based SARS-CoV-2 immunogen glycosylation reproducibly recapitulates signatures of viral glycosylation.