The evaluation of statins as potential inhibitors of the LEDGF/p75-HIV-1 integrase interaction

  • Chem Biol Drug Des. 2015 Mar;85(3):290-5. doi: 10.1111/cbdd.12384.
Angela T Harrison  1 ,  Frederik H Kriel ,  Maria A Papathanasopoulos ,  Salerwe Mosebi ,  Shaakira Abrahams ,  Raymond Hewer
Affiliations
  • 1. CMDD, Advanced Materials Division, Mintek, Private bag X3015, Randburg, Johannesburg, 2125, South Africa; HIV Pathogenesis Research Laboratory, Department of Molecular Medicine and Haematology, University of Witwatersrand Medical School, 7 York Road, Parktown, Johannesburg, 2193, South Africa.
PMID: 24954548 DOI: 10.1111/cbdd.12384
Abstract

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 (IC50 = 1.97 ± 0.45 μm) 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 μm). A correlation between lipophilicity and increased cellular toxicity of the statins was observed.

Keywords
AlphaScreen; HIV-1 integrase; LEDGF/p75; lovastatin; statins.