Site-specific steric control of SARS-CoV-2 spike glycosylation
Allen, J. D.; Chawla, H.; Samsudin, F.; Zuzic, L.; Shivgan, A. T.; Watanabe, Y.; He, W.-T.; Callaghan, S.; Song, G.; Yong, P.; Brouwer, P. J. M.; Song, Y.; Cai, Y.; Duyvesteyn, H. M. E.; Malinauskas, T.; Kint, J.; Pino, P.; Wurm, M. J.; Frank, M.; Chen, B.; Stuart, D. I.; Sanders, R. W.; Andrabi, R.; Burton, D. R.; Li, S.; Bond, P. J.; Crispin, M.
Show abstract
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.
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