Structural characterization of a serendipitously discovered bioactive macromolecule, lignin sulfate

Area of Science:

• Biochemistry
• Virology
• Polymer Science

Background:

• Herpes simplex virus-1 (HSV-1) infection relies on cell-surface heparan sulfate for cellular entry.
• Developing synthetic heparan sulfate mimics is a strategy to prevent HSV-1 infection.

Purpose of the Study:

• To identify potent inhibitors of HSV-1 infection by searching for synthetic heparan sulfate mimics.
• To characterize the active compound responsible for inhibiting HSV-1 infection.

Main Methods:

• Biophysical and chemical analyses were employed for compound identification.
• Mass spectrometry and elemental analysis characterized the lignin sulfate structure.
• High-performance size exclusion chromatography and polyacrylamide gel electrophoresis assessed molecular weight and polymer structure.

Main Results:

• Initial screening suggested a sulfated flavonoid inhibited HSV-1, but further analysis revealed the active component was a sulfated lignin polymer.
• Lignin sulfate, a polymer of p-coumaryl monomers linked by beta-O-4 linkages, was identified as the active principle.
• Characterization revealed a polydisperse polymer (1.5-40 kDa) with a highly networked structure, distinct from linear charged polymers.

Conclusions:

• Macromolecular lignin sulfate exhibits potent inhibitory activity against HSV-1 infection.
• Lignin sulfate's complex structure allows interactions with viral glycoproteins via hydrophobic, hydrogen-bonding, and ionic forces.
• Sulfated lignin represents a promising class of compounds with potential medicinal benefits for antiviral therapies.