Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12779/5064
Title: The anti-HIV activity of ADS-J1 targets the HIV-1 gp120
Authors: ARMAND UGON, M.
CLOTET CODINA, I.
Tintori, Cristina
Manetti, Fabrizio 
Clotet, B.
Botta, Maurizio 
Este, J. A.
Issue Date: 2005
Project: None 
Journal: VIROLOGY
Abstract: 
Recent data suggest that heparin sulfates may bind to a CD4 induced epitope in the HIV-1 gp120 that constitutes the coreceptor binding site. We have studied the mechanism of action of ADS-J1, a non-peptidic compound selected by docking analysis to interact with gp41 and to interfere with the formation of N-36/C-34 complexes in sandwich ELISA experiments. We show that ADS-J1 blocked the binding of wild-type HIV-1 NL4-3 strain to MT-4 cells but not virus-cell binding of a polyanion-resistant virus. However, ADS-J1 blocked the replication of polyanion-resistant, T-20- and C34-resistant HIV-1, suggesting a second mechanism of action. Development of resistance to ADS-J1 on the polyanion-resistant HIV-1 led to mutations in gp120 coreceptor binding site and not in gp41. Time of addition experiments confirmed that ADS-J1, but not polyanions such as dextran sulfate or AR177, worked at a step that mimics the activity of an HIV coreceptor antagonist but prior to gp41-dependent fusion. We conclude that ADS-J1 may bind to the HIV coreceptor binding site as its mechanism of anti-HIV activity.
Description: 
35302
URI: http://hdl.handle.net/20.500.12779/5064
ISSN: 0042-6822
DOI: 10.1016/j.virol.2005.08.007
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