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.
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Authors | Aurélia Galus, Jean-Maurice Mallet, David Lembo, Valeria Cagno, Madeleine Djabourov, Hugues Lortat-Jacob, Kawthar Bouchemal |
Journal | Carbohydrate polymers
(Carbohydr Polym)
Vol. 136
Pg. 113-20
(Jan 20 2016)
ISSN: 1879-1344 [Electronic] England |
PMID | 26572336
(Publication Type: Journal Article)
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Copyright | Copyright © 2015 Elsevier Ltd. All rights reserved. |
Chemical References |
- Amines
- Antiviral Agents
- alpha-Cyclodextrins
- Water
- Chondroitin Sulfates
- stearylamine
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Topics |
- Amines
(chemistry)
- Antiviral Agents
(chemistry, pharmacology)
- Carbohydrate Conformation
- Chemistry, Pharmaceutical
- Chondroitin Sulfates
(chemistry, pharmacology)
- Herpesvirus 2, Human
(drug effects)
- Hydrophobic and Hydrophilic Interactions
- Models, Molecular
- Structure-Activity Relationship
- Water
(chemistry)
- alpha-Cyclodextrins
(chemistry)
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