RT Journal Article
SR Electronic
T1 Analysis of the SARS-CoV-2 spike protein glycan shield: implications for immune recognition
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.04.07.030445
DO 10.1101/2020.04.07.030445
A1 Oliver C. Grant
A1 David Montgomery
A1 Keigo Ito
A1 Robert J. Woods
YR 2020
UL http://biorxiv.org/content/early/2020/05/01/2020.04.07.030445.abstract
AB 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 glycoform) the level of surface shielding is disproportionately high at 42%.Competing Interest StatementThe authors have declared no competing interest.