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

Supramolecular assemblies are of fundamental importance for cellular life and bio-interactive materials. The structure and function of these assemblies are decisively influenced by the design of their molecular components. In this work, we present a modular synthetic strategy for six novel bio-functional surfactants with a sulfonate headgroup (termed SupraVir surfactants). These amphiphilic molecules were designed for strong interactions with viral envelope proteins, virus inhibition, and to co-assemble water-soluble benzene-1,3,5-tricarboxamide derivatives (BTAs) to generate surfactant-grafted supramolecular polymers. Systematic spectroscopic and microscopic studies showed that the morphology of the co-assemblies strongly depends on the surfactant-BTA ratio. At surfactant ratios higher than 1, the native BTA nanofibers were disrupted, resulting in micellar architectures. In the test with herpes simplex virus (HSV-1), fibrous supramolecular polymers show significantly lower half-maximal inhibitory concentrations (IC50) compared to the corresponding micellar aggregates of the pure surfactants. Interestingly, the co-assemblies exhibited lower cytotoxicity than the functional surfactants alone, probably due to their structured incorporation into the polymeric scaffold. The dynamics of the co-assemblies, probed by hydrogen-deuterium exchange mass spectrometry (HDX-MS), showed correlations to the effectiveness. These results demonstrate a new co-assembly strategy of functional positioning antiviral surfactants in supramolecular scaffolds for the development of multivalent antiviral materials.