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Antimicrob Agents Chemother. 2012 Jan;56(1):154-62. doi: 10.1128/AAC.05595-11. Epub 2011 Nov 7.

Galectin-1-specific inhibitors as a new class of compounds to treat HIV-1 infection.

Author information

1
Glycobiology and Bioimaging Laboratory, Centre Hospitalier Universitaire de Québec-CHUL, and Faculté de Médecine, Université Laval, Quebec, Canada.

Abstract

Despite significant improvements, antiretroviral therapies against HIV-1 are plagued by a high frequency of therapeutic failures that have been associated with acquisition of drug resistance. We recently reported that HIV-1 exploits a host glycan binding protein, galectin-1, to increase its attachment to host cells, thereby increasing its overall infectivity in susceptible cells. This finding suggests that host molecules such as galectin-1 could reduce the expected efficiency of HIV-1 drugs targeting early steps of the replicative cycle, such as attachment and entry processes. Thus, new classes of drugs that would interfere with galectin-1/HIV-1 interactions could benefit the current antiretroviral therapy. To further explore this possibility, experiments were conducted to discover leading compounds showing specific inhibition of galectin-1 activity in a cellular model of HIV-1 infection. Three lactoside compounds were found to modestly inhibit the interaction of galectin-1 with primary human CD4(+) T cells. Interestingly, these same inhibitors reduced the galectin-1-mediated increase in HIV-1 attachment to target cells in a much more efficient manner. More important, the tested lactoside derivatives also significantly decreased the galectin-1-dependent enhancement of HIV-1 infection. These observations deserve further attention when considering that the development of new drugs to prevent and treat HIV-1 infection remains a priority.

PMID:
22064534
PMCID:
PMC3256073
DOI:
10.1128/AAC.05595-11
[Indexed for MEDLINE]
Free PMC Article

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