Journal
ANTIVIRAL RESEARCH
Volume 90, Issue 1, Pages 54-63Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.antiviral.2011.02.006
Keywords
HIV fusion inhibitor; gp41; Mammalian two-hybrid system; Small molecular compound
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Funding
- National Natural Science Foundation of China [30873107]
- Major State Basic Research Development Program of China (973 Program) [2009CB526513]
- State Key New Drug Creation and Manufacturing Program [2008ZX09401-005, 2009ZX9302-004, 2010ZX09401-403]
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gp41 is a major component of the envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) responsible for fusion of the viral envelope with the target cellular membrane. The formation of the trimer-of-hairpins core structure of gp41, via the interaction between its N-terminal heptad repeat (NHR) and its C-terminal heptad repeat (CHR) plays a key role in the membrane fusion process. Hence, inhibitors of trimer-of-hairpins formation have become a promising new class of HIV therapeutics. In the present study, based on the mammalian two-hybrid system, we developed a cell-based assay for detecting small-molecular HIV-1 fusion inhibitors targeting gp41. The optimized assay can be adapted to high-throughput screening in 96- and 384-well microplates with high signal-to-background ratios and acceptable Z' factors. The known small-molecular gp41 inhibitors, ADS-it, XTT formazan and tannin acid, tested positive in this assay, with half-maximal inhibitory concentration (IC50) values of 4.9 mu M, 5.6 mu M and 0.8 mu M, respectively. These data suggested that this novel assay is robust, sensitive and specific for identifying small-molecular HIV-1 gp41 inhibitors. (C) 2011 Elsevier B.V. All rights reserved.
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