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

Carbohydr Polym. 2016 Jan 20:136:113-20. doi: 10.1016/j.carbpol.2015.08.054. Epub 2015 Aug 20.

Abstract

The initial step in mucosal infection by the herpes simplex virus type 2 (HSV-2) requires its binding to certain glycosaminoglycans naturally present on host cell membranes. We took advantage of this interaction to design biomimetic supramolecular hexagonal-shaped nanoassemblies composed of chondroitin sulfate having exalted anti-HSV-2 activity in comparison with native chondroitin sulfate. Nanoassemblies were formed by mixing hydrophobically-modified chondroitin sulfate with α-cyclodextrin in water. Optimization of alkyl chain length grafted on chondroitin sulfate and the ratio between hydrophobically-modified chondroitin sulfate and α-cyclodextrin showed that more cohesive and well-structured nanoassemblies were obtained using higher α-cyclodextrin concentration and longer alkyl chain lengths. A structure-activity relationship was found between anti-HSV-2 activity and the amphiphilic nature of hydrophobically-modified chondroitin sulfate. Also, antiviral activity of hexagonal nanoassemblies against 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.

Keywords: Chondroitin sulfate; Entry inhibitor; Glycosaminoglycan; HSV-2; Nanoassembly.

MeSH terms

  • Amines / chemistry
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology*
  • Carbohydrate Conformation
  • Chemistry, Pharmaceutical
  • Chondroitin Sulfates / chemistry*
  • Chondroitin Sulfates / pharmacology*
  • Herpesvirus 2, Human / drug effects*
  • Hydrophobic and Hydrophilic Interactions
  • Models, Molecular
  • Structure-Activity Relationship
  • Water / chemistry
  • alpha-Cyclodextrins / chemistry

Substances

  • Amines
  • Antiviral Agents
  • alpha-Cyclodextrins
  • Water
  • Chondroitin Sulfates
  • stearylamine