2024-03-29T01:25:53Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/821542021-11-22T12:49:39Zcom_10261_81com_10261_5col_10261_334
François, K. O.
Pannecouque, C.
Auwerx, Johan
Lozano, V.
Peréz-Pérez, María-Jesús
Schols, D.
Balzarini, Jan
2009
Antimicrobial Agents and Chemotherapy 53: 4852- 4859 (2009)
http://hdl.handle.net/10261/82154
10.1128/AAC.00811-09
19721061
Alcian 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.
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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
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