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

Here we have generated 3D structures of glycoforms of the spike (S) protein SARS-CoV-2, based on reported 3D structures for the S protein and on reported glycomics data for the protein produced in HEK293 cells. We also report structures for glycoforms that represent those present in the nascent glycoproteins (prior to enzymatic modifications in the Golgi and ER), as well as those that are commonly observed on antigens present in other viruses. These models were subjected to MD simulation to take into account protein and glycan plasticity, and to determine the extent to which glycan microheterogeneity impacts antigenicity. Lastly, we have identified peptides in the S protein 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.

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