Molecular Details of the Recognition of Blood Group Antigens by a Human Norovirus as Determined by STD NMR Spectroscopy

Abstract

Der Infektion auf der Spur: Die Bindung von humanen Noroviruspartikeln an Blutgruppen‐Antigene wurde NMR‐spektroskopisch untersucht. Bindungsepitope wurden in atomarer Auflösung charakterisiert und Informationen zur Bindungsspezifität erhalten. Transferred‐NOE‐Experimente zeigen die biologisch aktive Konformation einzelner Zucker. Beides kann wichtige Informationen für das Design von Entry‐Inhibitoren gegen diese wichtige Gruppe humanpathogener Viren liefern.

Towards a Structural Basis for the Relationship Between Blood Group and the Severity of El Tor Cholera

“…Of course, proof for such a mechanism would require a detailed clinical study which could take other factors into account such as the secretor status of the patient. Nevertheless, our results further our understanding of the bloodgroup dependence of infectious disease, [26] while presenting new opportunities for developing anti-diarrheal therapies, or even the use of bacterial toxins to target cancers that overexpress Lewis-y oligosaccharides. [27] Received: December 22, 2011 Revised: March 6, 2012 Published online: April 5, 2012 .…”

Towards a Structural Basis for the Relationship Between Blood Group and the Severity of El Tor Cholera

“…Of course, proof for such a mechanism would require a detailed clinical study which could take other factors into account such as the secretor status of the patient. Nevertheless, our results further our understanding of the blood‐group dependence of infectious disease,26 while presenting new opportunities for developing anti‐diarrheal therapies, or even the use of bacterial toxins to target cancers that over‐express Lewis‐y oligosaccharides 27…”

Current tools for norovirus drug discovery

“…The experiments involved combining synthetic HBGA saccharides with norovirus VLP and monitoring the overall binding patterns with STD NMR spectroscopy. Binding was confirmed by the presence of STD signals, while absence of STD signals indicated no binding interaction [53]. L-Fructose was recognized by a binding pocket within the norovirus VLP and this binding pocket is highly conserved across a broad range of norovirus GII.4 strains.…”

“…Both polymer 1 and polymer 2 showed promise as entry-inhibitors and were found to have IC 50 values of 80 μM and 0.61 μM respectively [52]. STD NMR spectroscopy in conjunction with transfer NOESY experiments was used to investigate the binding of VLP of a GII.4 norovirus strain to HBGAs [53]. The experiments involved combining synthetic HBGA saccharides with norovirus VLP and monitoring the overall binding patterns with STD NMR spectroscopy.…”

“…L-Fructose was recognized by a binding pocket within the norovirus VLP and this binding pocket is highly conserved across a broad range of norovirus GII.4 strains. This suggests that the HBGA-fructose binding pocket is a promising target for the design of inhibitors that block viral entry into the host cells for infections with GII.4 [53].…”