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

Artikel i vetenskaplig tidskrift
Författare Joanna Said
Edward Trybala
Elin Andersson
Ken Johnstone
Ligong Liu
Norbert Wimmer
Vito Ferro
Tomas Bergström
Publicerad i Antiviral research
Volym 86
Nummer/häfte 3
Sidor 286-295
ISSN 1872-9096
Publiceringsår 2010
Publicerad vid Institutionen för biomedicin, avdelningen för infektionssjukdomar
Sidor 286-295
Språk en
Länkar dx.doi.org/10.1016/j.antiviral.2010...
Ämnesord HIV-1; HSV-2; Microbicides; Virucidal activity
Ämneskategorier Virologi

Sammanfattning

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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