Abstract
We have used NMR experiments to explore the binding of selected glycans and glycomimetics to the SARS CoV-2 spike glycoprotein (S-protein) and to its receptor binding domain (RBD). STD NMR experiments confirm the binding of sialoglycans to the S-protein of the prototypic Wuhan strain virus and yield dissociation constants in the millimolar range. The absence of STD effects for sialoglycans in the presence of the Omicron/BA.1 S-protein reflects a loss of binding as a result of S-protein evolution. Likewise, no STD effects are observed for the deletion mutant Δ143–145 of the Wuhan S-protein, thus supporting localization of the binding site in the N-terminal domain (NTD). The glycomimetics Oseltamivir and Zanamivir bind weakly to the S-protein of both virus strains. Binding of blood group antigens to the Wuhan S-protein cannot be confirmed by STD NMR. Using 1H,15N TROSY HSQC-based chemical shift perturbation (CSP) experiments, we excluded binding of any of the ligands studied to the RBD of the Wuhan S-protein. Our results put reported data on glycan binding into perspective and shed new light on the potential role of glycan-binding to the S-protein.
| Original language | English |
|---|---|
| Article number | e202202614 |
| Journal | Chemistry - A European Journal |
| Volume | 28 |
| Issue number | 71 |
| ISSN | 0947-6539 |
| DOIs | |
| Publication status | Published - 20.12.2022 |
Funding
T.P. thanks the State of Schleswig-Holstein for supplying the NMR infrastructure (European Funds for Regional Development, LPW-E/1.1.2/857). R.C. thanks the University of Lübeck for generous support. The state of Schleswig-Holstein is thanked for special funds within a program supporting SARS CoV-2 related projects. T.P. thanks the Deutsche Forschungsgemeinschaft (DFG) for grants Pe494/12-1 and Pe494/12-2 (FOR2327, ViroCarb). R.C. acknowledges funding by the Deutsche Forschungsgemeinschaft within the Walter Benjamin program (494746248). T.K. acknowledges funding by the BMBF (“NaFoUniMedCovid19“ (FKZ: 01KX2021)-COVIM) and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy-EXC 2155-project no. 390874280. We are grateful for computing time provided by BIOGNOS AB, Göteborg. Wilfried Hellebrandt (Lübeck) is thanked for synthesis of the H disaccharide. Open Access funding enabled and organized by Projekt DEAL. T.P. thanks the State of Schleswig‐Holstein for supplying the NMR infrastructure (European Funds for Regional Development, LPW‐E/1.1.2/857). R.C. thanks the University of Lübeck for generous support. The state of Schleswig‐Holstein is thanked for special funds within a program supporting SARS CoV‐2 related projects. T.P. thanks the Deutsche Forschungsgemeinschaft (DFG) for grants Pe494/12‐1 and Pe494/12‐2 (FOR2327, ViroCarb). R.C. acknowledges funding by the Deutsche Forschungsgemeinschaft within the Walter Benjamin program (494746248). T.K. acknowledges funding by the BMBF (“NaFoUniMedCovid19“ (FKZ: 01KX2021)‐COVIM) and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy‐EXC 2155‐project no. 390874280. We are grateful for computing time provided by BIOGNOS AB, Göteborg. Wilfried Hellebrandt (Lübeck) is thanked for synthesis of the H disaccharide. Open Access funding enabled and organized by Projekt DEAL.
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
- Centers: Center for Structural and Cell Biology (CSCM/ZMSZ)
DFG Research Classification Scheme
- 2.21-04 Virology
- 2.21-05 Immunology
Coronavirus related work
- Research on SARS-CoV-2 / COVID-19
