Site-specific steric control of SARS-CoV-2 spike glycosylation.
Joel D AllenHimanshi ChawlaFirdaus SamsudinLorena ZuzicAishwary Tukaram ShivganYasunori WatanabeWan-Ting HeSean CallaghanSophie Ge SongPeter YongPhilip J M BrouwerYutong SongYongfei CaiHelen M E DuyvesteynTomas MalinauskasJoeri KintPaco PinoFlorian M WurmMartin FrankBing ChenDavid I StuartRogier W SandersRaiees AndrabiDennis R BurtonSai LiPeter John BondMax CrispinPublished in: bioRxiv : the preprint server for biology (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 between 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 infectious virus S protein. We find patterns which are conserved across all samples and this can be associated with site-specific stalling of glycan maturation which act as a highly sensitive reporter of protein structure. Molecular dynamics (MD) simulations of a fully glycosylated spike support s 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.
Keyphrases
- sars cov
- molecular dynamics
- respiratory syndrome coronavirus
- density functional theory
- protein protein
- amino acid
- binding protein
- cell surface
- single cell
- cell free
- transcription factor
- coronavirus disease
- nitric oxide
- genome wide
- hydrogen peroxide
- dendritic cells
- microbial community
- risk assessment
- gene expression
- human health
- wastewater treatment
- high resolution