Supramolecular Polymer-Surfactant Co-Assemblies for Multivalent HSV-1 Inhibition

Area of Science:

• Supramolecular chemistry
• Materials science
• Virology

Background:

• Supramolecular assemblies are crucial for biological systems and biomaterials.
• Molecular design dictates the structure and function of these assemblies.
• Antiviral strategies require effective delivery and interaction with viral components.

Purpose of the Study:

• To synthesize novel bio-functional surfactants (SupraVir) for antiviral applications.
• To co-assemble these surfactants with benzene-1,3,5-tricarboxamide derivatives (BTAs) into supramolecular polymers.
• To investigate the antiviral efficacy and cytotoxicity of these novel co-assemblies.

Main Methods:

• Modular synthesis of six sulfonate-headed surfactants.
• Co-assembly with water-soluble BTAs.
• Spectroscopic and microscopic characterization of co-assemblies.
• Antiviral testing against herpes simplex virus (HSV-1).
• Hydrogen-deuterium exchange mass spectrometry (HDX-MS) for dynamics analysis.

Main Results:

• Co-assembly morphology (fibrous vs. micellar) depends on the surfactant-BTA ratio.
• Fibrous supramolecular polymers exhibited significantly lower IC50 values against HSV-1 than micellar aggregates.
• Co-assemblies showed lower cytotoxicity than pure surfactants, likely due to scaffold integration.
• HDX-MS revealed correlations between co-assembly dynamics and antiviral effectiveness.

Conclusions:

• A novel co-assembly strategy for positioning antiviral surfactants within supramolecular scaffolds was demonstrated.
• These findings pave the way for developing multivalent antiviral materials with enhanced efficacy and safety.
• The study highlights the potential of rationally designed supramolecular structures for combating viral infections.