Literature DB >> 23647983

Allosteric inhibition of HIV-1 integrase activity.

Alan Engelman1, Jacques J Kessl, Mamuka Kvaratskhelia.   

Abstract

HIV-1 integrase is an important therapeutic target in the fight against HIV/AIDS. Integrase strand transfer inhibitors (INSTIs), which target the enzyme active site, have witnessed clinical success over the past 5 years, but the generation of drug resistance poses challenges to INSTI-based therapies moving forward. Integrase is a dynamic protein, and its ordered multimerization is critical to enzyme activity. The integrase tetramer, bound to viral DNA, interacts with host LEDGF/p75 protein to tether integration to active genes. Allosteric integrase inhibitors (ALLINIs) that compete with LEDGF/p75 for binding to integrase disrupt integrase assembly with viral DNA and allosterically inhibit enzyme function. ALLINIs display steep dose response curves and synergize with INSTIs ex vivo, highlighting this novel inhibitor class for clinical development.
Copyright © 2013 Elsevier Ltd. All rights reserved.

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Year:  2013        PMID： 23647983      PMCID： PMC3679204          DOI： 10.1016/j.cbpa.2013.04.010

Source DB:  PubMed          Journal:  Curr Opin Chem Biol        ISSN： 1367-5931            Impact factor:   8.822


  40 in total

1.  Peptide inhibitors of HIV-1 integrase dissociate the enzyme oligomers.

Authors:  R G Maroun; S Gayet; M S Benleulmi; H Porumb; L Zargarian; H Merad; H Leh; J F Mouscadet; F Troalen; S Fermandjian
Journal:  Biochemistry       Date:  2001-11-20       Impact factor: 3.162

Review 2.  Allosteric inhibitor development targeting HIV-1 integrase.

Authors:  Laith Q Al-Mawsawi; Nouri Neamati
Journal:  ChemMedChem       Date:  2011-01-12       Impact factor: 3.466

Review 3.  Temporal changes in the epidemiology of transmission of drug-resistant HIV-1 across the world.

Authors:  Dineke Frentz; Charles A B Boucher; David A M C van de Vijver
Journal:  AIDS Rev       Date:  2012 Jan-Mar       Impact factor: 2.500

Review 4.  Evolution of HIV integrase resistance mutations.

Authors:  Peter K Quashie; Thibault Mesplède; Mark A Wainberg
Journal:  Curr Opin Infect Dis       Date:  2013-02       Impact factor: 4.915

5.  Discovery of small molecule HIV-1 integrase dimerization inhibitors.

Authors:  Cristina Tintori; Jonas Demeulemeester; Luigi Franchi; Silvio Massa; Zeger Debyser; Frauke Christ; Maurizio Botta
Journal:  Bioorg Med Chem Lett       Date:  2012-03-21       Impact factor: 2.823

Review 6.  Raltegravir: the first HIV-1 integrase strand transfer inhibitor in the HIV armamentarium.

Authors:  Bach-Yen T Nguyen; Robin D Isaacs; Hedy Teppler; Randi Y Leavitt; Peter Sklar; Marian Iwamoto; Larissa A Wenning; Michael D Miller; Joshua Chen; Ramon Kemp; Wei Xu; Robert A Fromtling; Joseph P Vacca; Steven D Young; Michael Rowley; Michael W Lower; Keith M Gottesdiener; Daria J Hazuda
Journal:  Ann N Y Acad Sci       Date:  2011-03       Impact factor: 5.691

7.  Differential effects of human immunodeficiency virus type 1 capsid and cellular factors nucleoporin 153 and LEDGF/p75 on the efficiency and specificity of viral DNA integration.

Authors:  Yasuhiro Koh; Xiaolin Wu; Andrea L Ferris; Kenneth A Matreyek; Steven J Smith; KyeongEun Lee; Vineet N KewalRamani; Stephen H Hughes; Alan Engelman
Journal:  J Virol       Date:  2012-10-24       Impact factor: 5.103

8.  HIV integration targeting: a pathway involving Transportin-3 and the nuclear pore protein RanBP2.

Authors:  Karen E Ocwieja; Troy L Brady; Keshet Ronen; Alyssa Huegel; Shoshannah L Roth; Torsten Schaller; Leo C James; Greg J Towers; John A T Young; Sumit K Chanda; Renate König; Nirav Malani; Charles C Berry; Frederic D Bushman
Journal:  PLoS Pathog       Date:  2011-03-10       Impact factor: 6.823

9.  Structural basis for functional tetramerization of lentiviral integrase.

Authors:  Stephen Hare; Francesca Di Nunzio; Alfred Labeja; Jimin Wang; Alan Engelman; Peter Cherepanov
Journal:  PLoS Pathog       Date:  2009-07-17       Impact factor: 6.823

10.  HRP-2 determines HIV-1 integration site selection in LEDGF/p75 depleted cells.

Authors:  Rik Schrijvers; Sofie Vets; Jan De Rijck; Nirav Malani; Frederic D Bushman; Zeger Debyser; Rik Gijsbers
Journal:  Retrovirology       Date:  2012-10-09       Impact factor: 4.602
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  38 in total

1.  Methods for the Analyses of Inhibitor-Induced Aberrant Multimerization of HIV-1 Integrase.

Authors:  Jacques J Kessl; Amit Sharma; Mamuka Kvaratskhelia
Journal:  Methods Mol Biol       Date:  2016

2.  Allosteric HIV Integrase Inhibitors Promote Formation of Inactive Branched Polymers via Homomeric Carboxy-Terminal Domain Interactions.

Authors:  Kushol Gupta; Audrey Allen; Carolina Giraldo; Grant Eilers; Robert Sharp; Young Hwang; Hemma Murali; Katrina Cruz; Paul Janmey; Frederic Bushman; Gregory D Van Duyne
Journal:  Structure       Date:  2020-12-23       Impact factor: 5.006

3.  Virtual screening of integrase inhibitors by large scale binding free energy calculations: the SAMPL4 challenge.

Authors:  Emilio Gallicchio; Nanjie Deng; Peng He; Lauren Wickstrom; Alexander L Perryman; Daniel N Santiago; Stefano Forli; Arthur J Olson; Ronald M Levy
Journal:  J Comput Aided Mol Des       Date:  2014-02-07       Impact factor: 3.686

4.  A critical role of the C-terminal segment for allosteric inhibitor-induced aberrant multimerization of HIV-1 integrase.

Authors:  Nikoloz Shkriabai; Venkatasubramanian Dharmarajan; Alison Slaughter; Jacques J Kessl; Ross C Larue; Lei Feng; James R Fuchs; Patrick R Griffin; Mamuka Kvaratskhelia
Journal:  J Biol Chem       Date:  2014-08-12       Impact factor: 5.157

5.  Preclinical profile of BI 224436, a novel HIV-1 non-catalytic-site integrase inhibitor.

Authors:  Craig Fenwick; Ma'an Amad; Murray D Bailey; Richard Bethell; Michael Bös; Pierre Bonneau; Michael Cordingley; René Coulombe; Jianmin Duan; Paul Edwards; Lee D Fader; Anne-Marie Faucher; Michel Garneau; Araz Jakalian; Stephen Kawai; Louie Lamorte; Steven LaPlante; Laibin Luo; Steve Mason; Marc-André Poupart; Nathalie Rioux; Patricia Schroeder; Bruno Simoneau; Sonia Tremblay; Youla Tsantrizos; Myriam Witvrouw; Christiane Yoakim
Journal:  Antimicrob Agents Chemother       Date:  2014-03-24       Impact factor: 5.191

Review 6.  Small-molecule inhibitors of protein-protein interactions: progressing toward the reality.

Authors:  Michelle R Arkin; Yinyan Tang; James A Wells
Journal:  Chem Biol       Date:  2014-09-18

7.  Critical Contribution of Tyr15 in the HIV-1 Integrase (IN) in Facilitating IN Assembly and Nonenzymatic Function through the IN Precursor Form with Reverse Transcriptase.

Authors:  Tatsuro Takahata; Eri Takeda; Minoru Tobiume; Kenzo Tokunaga; Masaru Yokoyama; Yu-Lun Huang; Atsuhiko Hasegawa; Tatsuo Shioda; Hironori Sato; Mari Kannagi; Takao Masuda
Journal:  J Virol       Date:  2016-12-16       Impact factor: 5.103

Review 8.  Host Factors in Retroviral Integration and the Selection of Integration Target Sites.

Authors:  Robert Craigie; Frederic D Bushman
Journal:  Microbiol Spectr       Date:  2014-12

9.  Improving Prediction Accuracy of Binding Free Energies and Poses of HIV Integrase Complexes Using the Binding Energy Distribution Analysis Method with Flattening Potentials.

Authors:  Junchao Xia; William Flynn; Ronald M Levy
Journal:  J Chem Inf Model       Date:  2018-07-03       Impact factor: 4.956

Review 10.  Development of Protein-Protein Interaction Inhibitors for the Treatment of Infectious Diseases.

Authors:  Andrew F Voter; James L Keck
Journal:  Adv Protein Chem Struct Biol       Date:  2017-08-24       Impact factor: 3.507
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