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)

目前的新冠肺炎大流行是由冠状病毒SARS-CoV2引起的，它像所有冠状病毒一样，利用病毒表面的“多糖保护膜”作为其感染途径的一部分。这种多聚糖屏障部分负责进入人类细胞，并保护其免受先天免疫系统的侵害。与其他人类冠状病毒分离株相比，SARS-CoV2变异株的糖蛋白外壳发生了一些重大变化，通过研究重组病毒刺突蛋白，它变得复杂起来，这些重组病毒刺突蛋白具有不同的糖蛋白屏蔽，具体取决于它们所在的细胞类型。目前的文献表明，受体结合区在该结构域的关键区域含有一个“O-糖链”。我们一起试图确定某个O-连接的糖链是否是受体结合域上的重要抗原决定因素。我们的建议是利用我们的专业知识在受体结合区的天然修饰氨基酸上设计一系列O-糖链，然后评估它们在SARS-CoV2病毒抗体反应中的作用。与PlantForm合作，我们将快速获得植物来源的SARS-CoV2刺突蛋白和分离的受体结构域。植物不添加O-葡聚糖，因此我们将完全控制我们安装在蛋白质上的O-葡聚糖，这样就可以确定这种多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.