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)

研究 O-聚糖对 SARS-CoV2 刺突蛋白受体结合域血清学的作用（COVID-19 大流行毒株）

• 批准号: 554628-2020
• 负责人: Wakarchuk, Warren
• 金额: $ 3.64万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Alliance Grants
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=705427
• 关键词: Investigation; role; glycan; serology; receptor

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.

当前的COVID-19大流行是由冠状病毒SARS-CoV2引起的，与所有冠状病毒一样，它利用病毒表面的“聚糖屏蔽”作为其感染途径的一部分。这种聚糖屏障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。与其他人类冠状病毒分离株相比，SARS-CoV2变体的聚糖屏蔽层发生了一些重大变化，而且由于研究重组病毒刺突蛋白根据制造它们的细胞类型具有不同的聚糖屏蔽层，情况变得更加复杂。目前的文献表明，受体结合区域在该区域的关键区域含有一个“o -聚糖”。我们共同寻求确定某个o链聚糖是否在受体结合域上是重要的抗原决定因素。我们的建议是利用我们的专业知识在受体结合域的天然修饰氨基酸上设计一个o -聚糖家族，然后评估它们在抗体对SARS-CoV2病毒的反应中的作用。与PlantForm合作，我们将能够快速获得植物衍生的SARS-CoV2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，从而可以确定该聚糖对抗体反应性的贡献的完整评估。