Hexagonal-shaped chondroitin sulfate self-assemblies have exalted anti-HSV-2 activity

The initial step in mucosal infection by the herpes simplex virus type 2 (HSV-2) requires its binding tocertain glycosaminoglycans naturally present on host cell membranes. We took advantage of this interac-tion to design biomimetic supramolecular hexagonal-shaped nanoassemblies composed of chondroitinsulfate having exalted anti-HSV-2 activity in comparison with native chondroitin sulfate. Nanoassem-blies were formed by mixing hydrophobically-modified chondroitin sulfate with -cyclodextrin in water.Optimization of alkyl chain length grafted on chondroitin sulfate and the ratio between hydrophobically-modified chondroitin sulfate and -cyclodextrin showed that more cohesive and well-structurednanoassemblies were obtained using higher -cyclodextrin concentration and longer alkyl chain lengths.A structure-activity relationship was found between anti-HSV-2 activity and the amphiphilic natureof hydrophobically-modified chondroitin sulfate. Also, antiviral activity of hexagonal nanoassembliesagainst HSV-2 was further improved in comparison with hydrophobically-modified chondroitin sulfate.This work suggests a new biomimetic formulation approach that can be extended to other heparan-sulfate-dependent viruses.