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bioRxiv · 10.1101/2020.04.07.030445

3D Models of glycosylated SARS-CoV-2 spike protein suggest challenges and opportunities for vaccine development

Grant, O. C.·Montgomery, D.·Ito, K.·Woods, R. J.
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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 glycoform) the level of surface shielding is disproportionately high at 42%.

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Grant, O. C., Montgomery, D., Ito, K., Woods, R. J.. 2020-04-09. 3D Models of glycosylated SARS-CoV-2 spike protein suggest challenges and opportunities for vaccine development. https://doi.org/10.1101/2020.04.07.030445

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