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Lipophile-conjugated sulfated oligosaccharides as novel microbicides against HIV-1.

Journal article
Authors Joanna Said
Edward Trybala
Elin Andersson
Ken Johnstone
Ligong Liu
Norbert Wimmer
Vito Ferro
Tomas Bergström
Published in Antiviral research
Volume 86
Issue 3
Pages 286-295
ISSN 1872-9096
Publication year 2010
Published at Institute of Biomedicine, Department of Infectious Medicine
Pages 286-295
Language en
Links dx.doi.org/10.1016/j.antiviral.2010...
Keywords HIV-1; HSV-2; Microbicides; Virucidal activity
Subject categories Virology

Abstract

With the aim of providing compounds suitable for further development as microbicides active against human immunodeficiency virus 1 (HIV-1) a library containing 37 lipophile-conjugated sulfated oligosaccharides was screened for antiviral and virucidal activity against this virus. Four highly active compounds had low drug inhibition concentrations (IC(50)) for HIV-1 and inactivated viral particles, suggestive of virucidal properties. Two of these compounds comprising a sulfated tetrasaccharide linked to a cholestanol group by a glycosidic bond, showed low toxicity and high selectivity indices. The two compounds were active both against CCR5 and dual-tropic CCR5/CXCR4 clinical HIV-1 isolates. Since herpes simplex virus type 2 (HSV-2) may be a cofactor for HIV-1 infection, the virucidal effect of the compounds was demonstrated against both viruses when mixed and incubated together on permissive cells. Incubation of compounds with serum, and to a lesser degree, cervical secretions, reduced the HIV-1 inactivating capacity, which suggests the need for molecular modification to reduce host protein binding. Considering the virucidal effect and low toxicity, these sulfated oligosaccharides with lipophilic tails may offer new possibilities of microbicide development.

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