A highly lipophilic sulfated tetrasaccharide glycoside related to muparfostat (PI-88) exhibits virucidal activity against herpes simplex virus

Ekblad, M, Adamiak, B, Bergstrom, T, Johnstone, KD, Karoli, T, Liu, LG, Ferro, V and Trybala, E (2010) A highly lipophilic sulfated tetrasaccharide glycoside related to muparfostat (PI-88) exhibits virucidal activity against herpes simplex virus. Antiviral Research, 86 2: 196-203. doi:10.1016/j.antiviral.2010.02.318


Author Ekblad, M
Adamiak, B
Bergstrom, T
Johnstone, KD
Karoli, T
Liu, LG
Ferro, V
Trybala, E
Title A highly lipophilic sulfated tetrasaccharide glycoside related to muparfostat (PI-88) exhibits virucidal activity against herpes simplex virus
Journal name Antiviral Research   Check publisher's open access policy
ISSN 0166-3542
1872-9096
Publication date 2010-05-01
Year available 2010
Sub-type Article (original research)
DOI 10.1016/j.antiviral.2010.02.318
Open Access Status DOI
Volume 86
Issue 2
Start page 196
End page 203
Total pages 8
Place of publication Netherlands
Publisher Elsevier Science Publishers
Language eng
Abstract Although sulfated polysaccharides potently inhibit the infectivity of herpes simplex virus (HSV) and human immunodeficiency virus in cultured cells, these compounds fail to show protective effects in humans, most likely due to their poor virucidal activity. Herein we report on sulfated oligosaccharide glycosides related to muparfostat (formerly known as PI-88) and their assessment for anti-HSV activity. Chemical modifications based on the introduction of specific hydrophobic groups at the reducing end of a sulfated oligosaccharide chain enhanced the compound's capability to inhibit the infection of cells by HSV-1 and HSV-2 and abrogated the cell-to-cell transmission of HSV-2. Furthermore, modification with a highly lipophilic cholestanyl group provided a compound with virucidal activity against HSV. This glycoside targeted the viral particle and, to a lesser degree, the cell, and exhibited an antiviral mode of action typical for sulfated polysaccharides and virucides, i.e., interference with the virus attachment to cells and irreversible inactivation of virus infectivity, respectively. The virucidal activity was decreased in the presence of human cervical secretions suggesting that higher doses of this glycoside might be needed for in vivo application. Altogether, the sulfated oligosaccharide-cholestanyl glycoside exhibits potent anti-HSV activity and is, therefore, a good candidate for development as a virucide. © 2010 Elsevier B.V.
Keyword Herpes simplex virus
Sulfated oligosaccharide glycosides
Virucidal activity
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Chemistry and Molecular Biosciences
 
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Created: Tue, 01 Mar 2011, 00:21:44 EST by Jennifer Falknau on behalf of School of Chemistry & Molecular Biosciences