Journal Article

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

Grant, Oliver C., Ito, Keigo, Montgomery, David, Woods, Robert J.

2020

Overview

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 innate and 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 notable 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 of the S trimer (17% for the HEK293 glycoform) they shield approximately 40% of the protein surface.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/114/2411 / 631/250 / ACE2 / Adaptive Immunity / Amino Acid Sequence / Angiotensin-Converting Enzyme 2 / Antibodies, Neutralizing - immunology / Antigen-Antibody Complex / Betacoronavirus - immunology / Betacoronavirus - isolation & purification / Betacoronavirus - metabolism / Binding Sites / Cadmium / Coronavirus Infections - immunology / Coronavirus Infections - pathology / Coronavirus Infections - virology / COVID-19 / Fourier analysis / Glycoproteins / Glycosylation / HEK293 Cells / HLA Antigens - metabolism / Humanities and Social Sciences / Humans / Immune response / Immunity, Innate / Molecular Dynamics Simulation / multidisciplinary / Nanotechnology / Pandemics / Peptides / Peptidyl-Dipeptidase A - chemistry / Peptidyl-Dipeptidase A - metabolism / Physicochemical properties / Pneumonia, Viral - immunology / Pneumonia, Viral - pathology / Pneumonia, Viral - virology / Polysaccharides - chemistry / Protein Binding / Protein Structure, Tertiary / SARS-CoV-2 / Scanning electron microscopy / Science / Science (multidisciplinary) / Sensors / Sequence Alignment / Severe acute respiratory syndrome coronavirus 2 / Spike Glycoprotein, Coronavirus - genetics / Spike Glycoprotein, Coronavirus - immunology / Spike Glycoprotein, Coronavirus - metabolism / Transmission electron microscopy / X-ray diffraction