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Title: The phtalocyanine prototype derivative Alcian Blue: the first synthetic agent with selective anti-human immunodeficiency virus activity due to its gp120 glycan-binding potential
Authors: François, Katrien O ×
Pannecouque, Christophe
Auwerx, Joeri
Lozano, Virginia
Pérez-Pérez, Maria-Jésus
Schols, Dominique
Balzarini, Jan #
Issue Date: Nov-2009
Publisher: American Society for Microbiology (ASM)
Series Title: Antimicrobial Agents and Chemotherapy vol:53 issue:11 pages:4852-4859
Abstract: Alcian Blue (AB), a phtalocyanine derivative, is able to prevent infection by a wide spectrum of HIV-1, HIV-2 and SIV strains in various cell types (T-cells, (co)receptor-transfected cells) and peripheral blood mononuclear cells. With the exception of herpes simpex virus, AB is inactive against a broad variety of other (DNA and RNA) viruses. Time-of-addition studies show that AB prevents HIV-1 infection at the virus entry stage, exactly at the same time as carbohydrate-binding agents (CBAs) do. AB also efficiently prevents fusion between persistently HIV-1-infected HUT-78 cells and uninfected (CD4(+)) lymphocytes, DC-SIGN-directed HIV-1 capture and subsequent transmission to uninfected (CD4(+)) T-lymphocytes. Prolonged passaging of HIV-1 at dose-escalating concentrations of AB resulted in the selection of mutant virus strains in which several N-glycans of the HIV-1 gp120 envelope are deleted and in which positively charged amino acid mutations in both gp120 and gp41 had appeared. A mutant virus strain in which four N-glycans were deleted showed a 10-fold decrease in sensitivity to the inhibitory effect of AB. These data suggest that AB is likely endowed with carbohydrate-binding properties and can be considered as an important lead compound in the development of novel synthetic non-peptidic antiviral drugs targeting the glycans of the envelope of HIV.
ISSN: 0066-4804
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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