Norovirus-glycan interactions - how strong are they really?

Area of Science:

• Virology
• Structural Biology
• Biochemistry

Background:

• Human norovirus (Norovirus) infection initiates with the major capsid protein VP1 binding to histo blood group antigens (HBGAs).
• Structural studies have elucidated the atomic details of VP1-HBGA interactions, specifically focusing on the protruding (P) domain dimers.
• Biophysical techniques like mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy are commonly employed to quantify these binding affinities.

Purpose of the Study:

• To investigate and explain the inconsistencies observed in reported binding affinities of norovirus capsid proteins to HBGAs.
• To compile reliable and reproducible binding affinity data for HBGA-glycan interactions.
• To demonstrate how combining MS and NMR techniques provides deeper insights into norovirus-host interactions.

Main Methods:

• Analysis of existing structural data for VP1-HBGA complexes.
• Critical evaluation of mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy methodologies for binding affinity determination.
• Compilation and cross-validation of binding affinity data from diverse studies.

Main Results:

• Significant discrepancies exist in binding affinity measurements for norovirus VP1-HBGA interactions between MS and NMR techniques.
• These inconsistencies stem from fundamental differences in how MS and NMR detect and quantify binding events.
• A curated dataset of reliable binding affinities is presented, validated through a combined MS and NMR approach.

Conclusions:

• The study resolves conflicting binding affinity data for norovirus-HBGA interactions by identifying sources of error in common biophysical methods.
• A reliable framework for measuring and interpreting norovirus-HBGA binding affinities is established.
• Integrated MS and NMR approaches offer a powerful strategy for understanding viral attachment mechanisms and developing antiviral interventions.