Glycans attaching to Noroviruses - Allosteric Cross talk meets post translational modification

• Applicant: Professor Dr. Thomas Peters
• Subject Area: Virology ; Biological and Biomimetic Chemistry ; Structural Biology
• Term: from 2016 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 269564371

Lately, we have used so-called ligand based NMR-techniques such as STD NMR to study carbohydrate binding to rabbit hemorrhagic disease virus (RHDV) and human noroviruses. We succeeded in synthesizing potent first generation entry inhibitors against human norovirus infection. A major drawback was the lack of cell culture systems, or animal models to further test the efficacy of these prototype inhibitors. Latest NMR studies in our laboratory suggest that binding of human noroviruses to histo-blood group antigens is much more complex than anticipated. We propose that this holds for all calicivirus-glycan interactions and has implications for virus entry. Therefore, we will apply our NMR methodology to study carbohydrate binding to murine noroviruses as a model system where cell culture systems and an animal model are available (Taube laboratory). Along with this we will identify molecular fragments that bind to murine noroviruses, and in collaboration with the Hartmann laboratory we will design and synthesize multivalent ligands for entry inhibition. These novel ligands will serve as tools to study molecular details of virus entry in vivo, and thus shine light on poorly understood aspects of the infection process. This work has the potential to uncover new strategies for the development of antiviral therapies.

• DFG Programme: Research Units
• Subproject of: FOR 2327: VIROCARB: Glycans Controlling Non-Enveloped Virus Infections