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The Evaluation of Statins as Potential Inhibitors of the LEDGF/p75–HIV‐1 Integrase interaction
Author(s) -
Harrison Angela T.,
Kriel Frederik H.,
Papathanasopoulos Maria A.,
Mosebi Salerwe,
Abrahams Shaakira,
Hewer Raymond
Publication year - 2015
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12384
Subject(s) - integrase , pravastatin , chemistry , lovastatin , lipophilicity , recombinant dna , integrase inhibitor , in vitro , human immunodeficiency virus (hiv) , biochemistry , pharmacology , virology , biology , antiretroviral therapy , cholesterol , dna , viral load , gene
Lovastatin was identified through virtual screening as a potential inhibitor of the LEDGF /p75– HIV ‐1 integrase interaction. In an AlphaScreen assay, lovastatin inhibited the purified recombinant protein–protein interaction ( IC 50 = 1.97 ± 0.45 μ m ) more effectively than seven other tested statins. None of the eight statins, however, yielded antiviral activity in vitro , while only pravastatin lactone yielded detectable inhibition of HIV ‐1 integrase strand transfer activity (31.65% at 100 μ m ). A correlation between lipophilicity and increased cellular toxicity of the statins was observed.