Site-specific steric control of SARS-CoV-2 spike glycosylation
Joel D Allen,
Aishwary Tukaram Shivgan,
Philip J.M. Brouwer,
Helen M E Duyvesteyn,
Maria J Wurm,
David I. Stuart,
Rogier W Sanders,
Dennis R. Burton,
Peter J Bond,
Posted 09 Mar 2021
bioRxiv DOI: 10.1101/2021.03.08.433764
Posted 09 Mar 2021
A central tenet in the design of recombinant vaccines is the display of native-like antigens in the elicitation of protective immunity. However, the diversity of global vaccine strategies against Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses challenges to benchmark antigens across global vaccine programs. Here, we investigate the glycosylation of a variety of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against the glycan shield of an infectious virus. The site-specific stalling of glycan maturation is a highly sensitive reporter of local protein structure and we find there is remarkable conservation of this feature across all samples. Analysis of molecular dynamics simulations of a fully glycosylated spike supports a model of steric restrictions that shape enzymatic processing of the glycans. Furthermore, we show that there is a conserved glycosylation pattern across the monomeric receptor binding domain (RBD) protein and the complete trimeric spike (S) protein. This is in contrast to RBD glycosylation in Middle East respiratory syndrome coronavirus (MERS-CoV) where quaternary architecture limits glycan processing when in the context of full-length MERS-CoV S protein. These results suggest that spike-based immunogen glycosylation reproducibly recapitulates viral glycosylation.
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