title: Inhibition Profiling of Retroviral Protease Inhibitors Using an HIV-2 Modular System.
abstract: Retroviral protease inhibitors (PIs) are fundamental pillars in the treatment of HIV infection and acquired immunodeficiency syndrome (AIDS). Currently used PIs are designed against HIV-1, and their effect on HIV-2 is understudied. Using a modular HIV-2 protease cassette system, inhibition profiling assays were carried out for protease inhibitors both in enzymatic and cell culture assays. Moreover, the treatment-associated resistance mutations (I54M, L90M) were introduced into the modular system, and comparative inhibition assays were performed to determine their effect on the susceptibility of the protease. Our results indicate that darunavir, saquinavir, indinavir and lopinavir were very effective HIV-2 protease inhibitors, while tipranavir, nelfinavir and amprenavir showed a decreased efficacy. I54M, L90M double mutation resulted in a significant reduction in the susceptibility to most of the inhibitors with the exception of tipranavir. To our knowledge, this modular system constitutes a novel approach in the field of HIV-2 protease characterization and susceptibility testing.
authors.affiliation: Laboratory of Retroviral Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, H-4010 Debrecen, Hungary. mohamed@med.unideb.hu.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Mahdi
authors.affiliation: Laboratory of Retroviral Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, H-4010 Debrecen, Hungary. atiem3@gmail.com.
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Szojka
authors.affiliation: Laboratory of Retroviral Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, H-4010 Debrecen, Hungary. motyan.janos@med.unideb.hu.
authors.forename: János András
authors.initials: JA
authors.lastname: Mótyán
authors.affiliation: Laboratory of Retroviral Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, H-4010 Debrecen, Hungary. tozser@med.unideb.hu.
authors.forename: József
authors.initials: J
authors.lastname: Tőzsér
mesh_terms: D019380:Anti-HIV Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D017320:HIV Protease Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D015498:HIV-2 / Q000187:drug effects*; D006801:Humans
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors
keywords: HIV-2; modular system; protease; protease inhibitors; susceptibility