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

被引：25

作者：

Galus, Aurelia ^{[1
]}

Mallet, Jean-Maurice ^{[2
]}

Lembo, David ^{[3
]}

Cagno, Valeria ^{[3
]}

Djabourov, Madeleine ^{[4
]}

Lortat-Jacob, Hugues ^{[5
]}

Bouchemal, Kawthar ^{[6
]}

机构：

[1] Univ Paris 11, Fac Pharm, UMR CNRS 8612, Inst Galien Paris Sud, F-92290 Chatenay Malabry, France

[2] Univ Paris 06, Ecole Normale Super, Dept Chim, CNRS UMR LBM 7203, F-75005 Paris, France

[3] Univ Turin, Dept Clin & Biol Sci, Turin, Italy

[4] PSL Res Univ, ESPCI ParisTech, Lab Phys Therm, F-75231 Paris 5, France

[5] Univ Grenoble Alpes, Inst Biol Struct, CNRS, CEA,UMR5075, F-38044 Grenoble, France

[6] Univ Paris 11, Fac Pharm, UMR CNRS 8612, Inst Univ France,Inst Galien Paris Sud, F-92290 Chatenay Malabry, France

来源：

CARBOHYDRATE POLYMERS | 2016年 / 136卷

关键词：

HSV-2; Glycosaminoglycan; Chondroitin sulfate; Nanoassembly; Entry inhibitor; HERPES-SIMPLEX-VIRUS; HEPARAN-SULFATE; CRYSTAL; BINDING; COMPLEX; PLAYS; CELLS;

D O I：

10.1016/j.carbpol.2015.08.054

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

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 alpha-cyclodextrin in water. Optimization of alkyl chain length grafted on chondroitin sulfate and the ratio between hydrophobically-modified chondroitin sulfate and alpha-cyclodextrin showed that more cohesive and well-structured nanoassemblies were obtained using higher alpha-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 heparansulfate-dependent viruses. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：113 / 120

页数：8