Targeting norovirus infection - Multivalent entry inhibitor design based on NMR experiments

Christoph Rademacher, Julie Guiard, Pavel I. Kitov, Brigitte Fiege, Kevin P. Dalton, Francisco Parra, David R. Bundle, Thomas Peters*

*Corresponding author for this work
52 Citations (Scopus)


Noroviruses attach to their host cells through histo blood group antigens (HBGAs), and compounds that interfere with this interaction are likely to be of therapeutic or diagnostic interest. It is shown that NMR binding studies can simultaneously identify and differentiate the site for binding HBGA ligands and complementary ligands from a large compound library, thereby facilitating the design of potent heterobifunctional ligands. Saturation transfer difference (STD) NMR experiments, spin-lock filtered NMR experiments, and interligand NOE (ILOE) experiments in the presence of virus-like particles (VLPs), identified compounds that bind to the HBGA binding site of human norovirus. Based on these data two multivalent prototype entry-inhibitors against norovirus infection were synthesized. A surface plasmon resonance based inhibition assay showed avidity gains of 1000 and one million fold over a millimolar univalent ligand. This suggests that further rational design of multivalent inhibitors based on our strategy will identify potent entry-inhibitors against norovirus infections.

Original languageEnglish
JournalChemistry - A European Journal
Issue number27
Pages (from-to)7442-7453
Number of pages12
Publication statusPublished - 27.06.2011

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


Dive into the research topics of 'Targeting norovirus infection - Multivalent entry inhibitor design based on NMR experiments'. Together they form a unique fingerprint.

Cite this