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

• Applicant: Dr. Thomas Rexer
• Subject Area: Virology
• Term: from 2021 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 458633485

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.

• DFG Programme: Research Grants
• Cooperation Partner: Professorin Dr. Dunja Bruder