Deciphering the impact of Sars-CoV-2 envelope protein glycosylation on human pathogenicity

解读 Sars-CoV-2 包膜蛋白糖基化对人类致病性的影响

• 批准号: 458633485
• 负责人: Dr. Thomas Rexer
• 金额: --
• 依托单位: Institut für Medizinische Mikrobiologie und Krankenhaushygiene
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2021
• 资助国家: 德国
• 起止时间: 2020-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/458633485?language=en
• 关键词: Deciphering; impact; Sars; CoV; envelope

The ongoing corona virus disease 2019 (Covid-19) pandemic is caused by the coronavirus Sars-CoV-2. Viral entry into human host cells is mediated by the glycoprotein Spike S that binds to angiotensin-converting enzyme 2 (ACE2). Compared to other viral membrane proteins Spike S is heavily N-glycosylated. For other viruses, it has been shown previously that glycosylation significantly impacts antibody response and neutralizing antibody levels. We hypothesize that the glycosylation and the glycoforms of the Spike S of Sars-CoV-2 has a severe impact on its human-pathogenic features and consequently needs to be considered to support future development of improved vaccines and novel therapeutics. Objective of the project is to produce recombinant Sars-CoV-2 Spike S in insect cells and use the synthetic glycobiotechnology platform developed at the MPI to generate differentially glycosylated Spike S as well as deglycosylated Spike S. The platform consists of cascades of recombinant glycosyltransferase that enables us to tailor the N-glycosylation of protein in one-pot reactions. The Spike S proteins with different glycoforms will be investigated for binding to ACE 2 and the immune response in mice by our project partner - the Otto-von-Guericke-University Magdeburg.

持续的2019冠状病毒病（Covid-19）大流行是由冠状病毒SARS-CoV-2引起的。病毒进入人类宿主细胞由糖蛋白Spike S介导，该糖蛋白与血管紧张素转化酶2（ACE 2）结合。与其他病毒膜蛋白相比，Spike S是高度N-糖基化的。对于其他病毒，先前已显示糖基化显著影响抗体应答和中和抗体水平。我们假设，糖基化和糖型的刺突S的SARS冠状病毒-2有一个严重的影响，其人类致病性的特点，因此需要考虑支持未来的发展，改进的疫苗和新的治疗方法。该项目的目的是在昆虫细胞中生产重组Sars-CoV-2 Spike S，并使用MPI开发的合成糖生物技术平台生产差异糖基化Spike S以及去糖基化Spike S。该平台由重组糖基转移酶的级联组成，使我们能够在一锅反应中定制蛋白质的N-糖基化。我们的项目合作伙伴--奥托-冯-格里克大学马格德堡将研究具有不同糖型的Spike S蛋白与ACE 2的结合以及小鼠的免疫应答。