Potent anti-respiratory syncytial virus activity of a cholestanol-sulfated tetrasaccharide conjugate

Lundin, Anna, Bergstrom, Tomas, Andrighetti-Fröhner, Carla R., Bendrioua, Loubna, Ferro, Vito and Trybala, Edward (2012) Potent anti-respiratory syncytial virus activity of a cholestanol-sulfated tetrasaccharide conjugate. Antiviral Research, 93 1: 101-109. doi:10.1016/j.antiviral.2011.11.002


Author Lundin, Anna
Bergstrom, Tomas
Andrighetti-Fröhner, Carla R.
Bendrioua, Loubna
Ferro, Vito
Trybala, Edward
Total Author Count Override 6
Title Potent anti-respiratory syncytial virus activity of a cholestanol-sulfated tetrasaccharide conjugate
Journal name Antiviral Research   Check publisher's open access policy
ISSN 0166-3542
1872-9096
Publication date 2012-01
Year available 2011
Sub-type Article (original research)
DOI 10.1016/j.antiviral.2011.11.002
Volume 93
Issue 1
Start page 101
End page 109
Total pages 9
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Collection year 2013
Language eng
Formatted abstract
A number of different viruses including respiratory syncytial virus (RSV) initiate infection of cells by binding to cell surface glycosaminoglycans and sulfated oligo- and polysaccharide mimetics of these receptors exhibit potent antiviral activity in cultured cells. We investigated whether the introduction of different lipophilic groups to the reducing end of sulfated oligosaccharides would modulate their anti-RSV activity. Our results demonstrate that the cholestanol-conjugated tetrasaccharide (PG545) exhibited ∼5- to 16-fold enhanced anti-RSV activity in cultured cells compared with unmodified sulfated oligosaccharides. Furthermore, PG545 displayed virus-inactivating (virucidal) activity, a feature absent in sulfated oligosaccharides. To inhibit RSV infectivity PG545 had to be present during the initial steps of viral infection of cells. The anti-RSV activity of PG545 was due to both partial inhibition of the virus attachment to cells and a more profound interference with some post-attachment steps as PG545 efficiently neutralized infectivity of the cell-adsorbed virus. The anti-RSV activity of PG545 was reduced when tested in the presence of human nasal secretions. Serial passages of RSV in the presence of increasing concentrations of PG545 selected for weakly resistant viral variants that comprised the F168S and the P180S amino acid substitutions in the viral G protein. Altogether we identified a novel and potent inhibitor of RSV, which unlike sulfated oligo- and polysaccharide compounds, could irreversibly inactivate RSV infectivity.
Keyword Respiratory syncytial virus
PG545
Sulfated oligosaccharides
Virucidal activity
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 15 November 2011

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Wed, 04 Jan 2012, 08:55:15 EST by Lucy O'Brien on behalf of School of Chemistry & Molecular Biosciences