The anti-HIV activity of ADS-J1 targets the HIV-1 gp120

Mercedes Armand-Ugón, Imma Clotet-Codina, Cristina Tintori, Fabrizio Manetti, Bonaventura Clotet, Maurizio Botta, José A. Esté

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42 Citations (Scopus)

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. © 2005 Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)141-149
JournalVirology
Volume343
Issue number1
DOIs
Publication statusPublished - 5 Dec 2005

Keywords

  • Drug resistance
  • Entry
  • Fusion
  • gp120
  • gp41
  • HIV-1

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