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)

目前的COVID-19大流行是由冠状病毒SARS-CoV 2引起的，与所有冠状病毒一样，它利用病毒表面的“聚糖盾”作为其感染途径的一部分。这种聚糖盾部分负责进入人体细胞，并保护其免受先天免疫系统的侵害。SARS-CoV 2变异体相对于其他人类CoV分离株的聚糖屏蔽有一些显着的变化-并且通过研究具有不同聚糖屏蔽的重组病毒刺突蛋白，这取决于它们产生的细胞类型，这是复杂的。目前的文献表明受体结合结构域在该结构域的关键区域中含有“0-聚糖”。我们一起寻求确定是否某个O-连接的聚糖是受体结合结构域上的重要抗原决定簇。我们的建议是利用我们的专业知识，在受体结合结构域中天然修饰的氨基酸上设计一个O-聚糖家族，然后评估它们在SARS-CoV 2病毒抗体应答中的作用。与PlantForm合作，我们将快速获得植物来源的SARS-CoV 2刺突蛋白和分离的受体结构域。植物不添加O-聚糖，因此我们将完全控制我们安装在蛋白质上的O-聚糖，以便可以确定该聚糖对抗体反应性的贡献的完整评估。

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.