Analysis of the SARS-CoV-2 spike protein glycan shield: implications for immune recognition

BioRxiv : the Preprint Server for Biology
Oliver C GrantRobert J Woods

Abstract

Here we have generated 3D structures of glycoforms of the spike (S) glycoprotein from SARS-CoV-2, based on reported 3D structures and glycomics data for the protein produced in HEK293 cells. We also analyze structures for glycoforms representing those present in the nascent glycoproteins (prior to enzymatic modifications in the Golgi), as well as those that are commonly observed on antigens present in other viruses. These models were subjected to molecular dynamics (MD) simulation to determine the extent to which glycan microheterogeneity impacts the antigenicity of the S glycoprotein. Lastly, we have identified peptides in the S glycoprotein that are likely to be presented in human leukocyte antigen (HLA) complexes, and discuss the role of S protein glycosylation in potentially modulating the adaptive immune response to the SARS-CoV-2 virus or to a related vaccine. The 3D structures show that the protein surface is extensively shielded from antibody recognition by glycans, with the exception of the ACE2 receptor binding domain, and also that the degree of shielding is largely insensitive to the specific glycoform. Despite the relatively modest contribution of the glycans to the total molecular weight (17% for the HEK293 glycof...Continue Reading

Citations

Jun 7, 2020·Glycoconjugate Journal·Roberto Adamo, Sandro Sonnino
Dec 29, 2020·Frontiers in Physiology·Tales Lyra OliveiraRobinson Sabino-Silva
Jun 11, 2021·Frontiers in Molecular Biosciences·Sonia Beeckmans, Edilbert Van Driessche
Jun 16, 2021·Genome Medicine·Christof C SmithAlex Rubinsteyn
Jun 18, 2021·Frontiers in Molecular Biosciences·Arnaud John Kombe KombeTengchuan Jin
Jun 20, 2020·The Journal of Physical Chemistry. B·Hyeonuk WooWonpil Im
Nov 4, 2020·ACS Central Science·Lorenzo CasalinoRommie E Amaro

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Methods Mentioned

BETA
glycosylation
NMR

Software Mentioned

Amber14
MODEL
PMEMD
Visual Molecular Dynamics ( VMD )
GLYCAM06
AMBER
SWISS
RankPep

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