title: The evaluation of statins as potential inhibitors of the LEDGF/p75-HIV-1 integrase interaction.
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.
authors: 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.
authors: Angela T
authors: AT
authors: Harrison
authors: Frederik H
authors: FH
authors: Kriel
authors: Maria A
authors: MA
authors: Papathanasopoulos
authors: Salerwe
authors: S
authors: Mosebi
authors: Shaakira
authors: S
authors: Abrahams
authors: Raymond
authors: R
authors: Hewer
mesh_terms: D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D019427:HIV Integrase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000201:enzymology / Q000502:physiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008148:Lovastatin / Q000737:chemistry / Q000494:pharmacology; D054730:Protein Interaction Domains and Motifs / Q000187:drug effects; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019428:HIV Integrase Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; C119380:lens epithelium-derived growth factor; D008148:Lovastatin; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1
keywords: AlphaScreen; HIV-1 integrase; LEDGF/p75; lovastatin; statins