title: Hexagonal-shaped chondroitin sulfate self-assemblies have exalted anti-HSV-2 activity.
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.
authors.affiliation: Institut Galien Paris Sud, UMR CNRS 8612, Faculté de Pharmacie, Univ Paris-Sud, Châtenay-Malabry Cedex, France.
authors.forename: Aurélia
authors.initials: A
authors.lastname: Galus
authors.affiliation: École Normale Supérieure, Département de Chimie, UPMC Univ Paris 06, CNRS UMR 7203 LBM, 24, rue Lhomond, 75005 Paris, France.
authors.forename: Jean-Maurice
authors.initials: JM
authors.lastname: Mallet
authors.affiliation: University of Turin, Department of Clinical and Biological Sciences, Torino, Italy.
authors.forename: David
authors.initials: D
authors.lastname: Lembo
authors.affiliation: University of Turin, Department of Clinical and Biological Sciences, Torino, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Cagno
authors.affiliation: Laboratoire de Physique Thermique, ESPCI ParisTech, PSL Research University, 10 Rue Vauquelin, 75231 Paris, Cedex 5, France.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Djabourov
authors.affiliation: Institut de Biologie Structurale, Université Grenoble-Alpes, CNRS, CEA, UMR5075, 38044 Grenoble, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: Lortat-Jacob
authors.affiliation: Institut Universitaire de France, Institut Galien Paris Sud, UMR CNRS 8612, Faculté de Pharmacie, Univ Paris-Sud, Châtenay-Malabry Cedex, France. Electronic address: kawthar.bouchemal@u-psud.fr.
authors.forename: Kawthar
authors.initials: K
authors.lastname: Bouchemal
mesh_terms: D000588:Amines / Q000737:chemistry; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D002236:Carbohydrate Conformation; D002626:Chemistry, Pharmaceutical; D002809:Chondroitin Sulfates / Q000737:chemistry* / Q000494:pharmacology*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry; D047391:alpha-Cyclodextrins / Q000737:chemistry
chemical_list: D000588:Amines; D000998:Antiviral Agents; D047391:alpha-Cyclodextrins; D014867:Water; D002809:Chondroitin Sulfates; C009317:stearylamine
keywords: Chondroitin sulfate; Entry inhibitor; Glycosaminoglycan; HSV-2; Nanoassembly