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Title

The phthalocyanine prototype derivative Alcian blue is the first synthetic agent with selective anti-human immunodeficiency virus activity due to its gp120 glycan-binding potential

AuthorsFrançois, K. O.; Pannecouque, C.; Auwerx, Johan; Lozano, V. ; Peréz-Pérez, María-Jesús ; Schols, D.; Balzarini, Jan
Issue Date2009
PublisherAmerican Society for Microbiology
CitationAntimicrobial Agents and Chemotherapy 53: 4852- 4859 (2009)
AbstractAlcian Blue (AB), a phthalocyanine derivative, is able to prevent infection by a wide spectrum of human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus strains in various cell types [T cells, (co)receptor-transfected cells, and peripheral blood mononuclear cells]. With the exception of herpes simplex 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 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 were deleted and in which positively charged amino acid mutations in both gp120 and gp41 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 an important lead compound in the development of novel synthetic nonpeptidic antiviral drugs targeting the glycans of the envelope of HIV. Copyright © 2009, American Society for Microbiology. All Rights Reserved.
URIhttp://hdl.handle.net/10261/82154
DOIhttp://dx.doi.org/10.1128/AAC.00811-09
Identifiersdoi: 10.1128/AAC.00811-09
issn: 0066-4804
e-issn: 1098-6596
Appears in Collections:(IQM) Artículos
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