Investigation the role of the O-glycan on the serology of the receptor binding domain of the SARS-CoV2 spike protein (COVID-19 pandemic strain)

Wakarchuk, Warren | $50,000

Alberta University of Alberta 2020 NSERC Alliance COVID-19 Grant

The current COVID‑19 pandemic is caused by the corona virus, SARS-CoV2, which like all corona viruses exploits a viral surface “glycan shield” as part of its infectious path. This glycan shield is partly responsible for the entry into human cells, and protection from the innate immune system. The SARS-CoV2 variant has some significant changes to its glycan shield relative to other human CoV isolates – and it is complicated by studying recombinant viral spike proteins having different glycan shield depending on the cell type they were made in. Current literature suggests the receptor binding domain contains an “O-glycan” in a critical region of this domain. Together we seek to identify if a certain O-linked glycan is important antigenic determinant on the receptor binding domain. Our proposal is to use our expertise to engineer a family of O-glycans on the naturally modifed amino acid in the receptor binding domain and then to evaluate their role in the antibody response to the SARS-CoV2 virus. Teaming up with PlantForm we will have rapid access to plant derived SARS-CoV2 spike protein, and the isolated receptor domain. Plants do not add O-glycans, so we will have complete control of the O-glycan we install on the proteins such that a complete evaluation of the contribution from this glycan to antibody reactivity can be determined.

With funding from the Government of Canada

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