Literature DB >> 26747394

Identification of a small molecule HIV-1 inhibitor that targets the capsid hexamer.

Jimmy P Xu1, Jeffrey D Branson1, Rae Lawrence2, Simon Cocklin3.   

Abstract

The HIV-1 CA protein is an attractive therapeutic target for the development of new antivirals. An inter-protomer pocket within the hexamer configuration of the CA, which is a binding site for key host dependency factors, is an especially appealing region for small molecule targeting. Using a field-based pharmacophore derived from an inhibitor known to interact with this region, coupled to biochemical and biological assessment, we have identified a new compound that inhibits HIV-1 infection and that targets the assembled CA hexamer.
Copyright © 2015 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  Antiviral; Computer-aided drug design; Field-based virtual screening; HIV-1 capsid protein; Surface plasmon resonance

Mesh：

Substances：

Year:  2015        PMID： 26747394      PMCID： PMC4728034          DOI： 10.1016/j.bmcl.2015.12.087

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  30 in total

1.  Structures of the HIV-1 capsid protein dimerization domain at 2.6 A resolution.

Authors:  D K Worthylake; H Wang; S Yoo; W I Sundquist; C P Hill
Journal:  Acta Crystallogr D Biol Crystallogr       Date:  1999-01-01

2.  Implications for viral capsid assembly from crystal structures of HIV-1 Gag(1-278) and CA(N)(133-278).

Authors:  Brian N Kelly; Bruce R Howard; Hui Wang; Howard Robinson; Wesley I Sundquist; Christopher P Hill
Journal:  Biochemistry       Date:  2006-09-26       Impact factor: 3.162

Review 3.  Capsid (CA) protein as a novel drug target: recent progress in the research of HIV-1 CA inhibitors.

Authors:  Jiyan Zhang; Xinyong Liu; Erik De Clercq
Journal:  Mini Rev Med Chem       Date:  2009-04       Impact factor: 3.862

Review 4.  The structural biology of HIV assembly.

Authors:  Barbie K Ganser-Pornillos; Mark Yeager; Wesley I Sundquist
Journal:  Curr Opin Struct Biol       Date:  2008-04-09       Impact factor: 6.809

5.  FieldScreen: virtual screening using molecular fields. Application to the DUD data set.

Authors:  Timothy J Cheeseright; Mark D Mackey; James L Melville; Jeremy G Vinter
Journal:  J Chem Inf Model       Date:  2008-11       Impact factor: 4.956

6.  Solution structure of a hydrocarbon stapled peptide inhibitor in complex with monomeric C-terminal domain of HIV-1 capsid.

Authors:  Shibani Bhattacharya; Hongtao Zhang; Asim K Debnath; David Cowburn
Journal:  J Biol Chem       Date:  2008-04-16       Impact factor: 5.157

7.  Crystal structure of human cyclophilin A bound to the amino-terminal domain of HIV-1 capsid.

Authors:  T R Gamble; F F Vajdos; S Yoo; D K Worthylake; M Houseweart; W I Sundquist; C P Hill
Journal:  Cell       Date:  1996-12-27       Impact factor: 41.582

8.  Structure of the antiviral assembly inhibitor CAP-1 complex with the HIV-1 CA protein.

Authors:  Brian N Kelly; Sampson Kyere; Isaac Kinde; Chun Tang; Bruce R Howard; Howard Robinson; Wesley I Sundquist; Michael F Summers; Christopher P Hill
Journal:  J Mol Biol       Date:  2007-08-15       Impact factor: 5.469

9.  X-ray structures of the hexameric building block of the HIV capsid.

Authors:  Owen Pornillos; Barbie K Ganser-Pornillos; Brian N Kelly; Yuanzi Hua; Frank G Whitby; C David Stout; Wesley I Sundquist; Christopher P Hill; Mark Yeager
Journal:  Cell       Date:  2009-06-11       Impact factor: 41.582

10.  Structure of full-length HIV-1 CA: a model for the mature capsid lattice.

Authors:  Barbie K Ganser-Pornillos; Anchi Cheng; Mark Yeager
Journal:  Cell       Date:  2007-10-05       Impact factor: 41.582
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  12 in total

1.  Exploring Modifications of an HIV-1 Capsid Inhibitor: Design, Synthesis, and Mechanism of Action.

Authors:  Jimmy P Xu; Ashwanth C Francis; Megan E Meuser; Marie Mankowski; Roger G Ptak; Adel A Rashad; Gregory B Melikyan; Simon Cocklin
Journal:  J Drug Des Res       Date:  2018-08-13

2.  Design, synthesis, and mechanism study of dimerized phenylalanine derivatives as novel HIV-1 capsid inhibitors.

Authors:  Xujie Zhang; Lin Sun; Megan E Meuser; Waleed A Zalloum; Shujing Xu; Tianguang Huang; Srinivasulu Cherukupalli; Xiangyi Jiang; Xiao Ding; Yucen Tao; Dongwei Kang; Erik De Clercq; Christophe Pannecouque; Alexej Dick; Simon Cocklin; Xinyong Liu; Peng Zhan
Journal:  Eur J Med Chem       Date:  2021-09-16       Impact factor: 7.088

3.  Design, synthesis, and mechanistic investigations of phenylalanine derivatives containing a benzothiazole moiety as HIV-1 capsid inhibitors with improved metabolic stability.

Authors:  Shujing Xu; Lin Sun; Alexej Dick; Waleed A Zalloum; Tianguang Huang; Megan E Meuser; Xujie Zhang; Yucen Tao; Srinivasulu Cherukupalli; Dang Ding; Xiao Ding; Shenghua Gao; Xiangyi Jiang; Dongwei Kang; Erik De Clercq; Christophe Pannecouque; Simon Cocklin; Xinyong Liu; Peng Zhan
Journal:  Eur J Med Chem       Date:  2021-10-09       Impact factor: 7.088

4.  Design, Synthesis, and Mechanism Study of Benzenesulfonamide-Containing Phenylalanine Derivatives as Novel HIV-1 Capsid Inhibitors with Improved Antiviral Activities.

Authors:  Lin Sun; Alexej Dick; Megan E Meuser; Tianguang Huang; Waleed A Zalloum; Chin-Ho Chen; Srinivasulu Cherukupalli; Shujing Xu; Xiao Ding; Ping Gao; Dongwei Kang; Erik De Clercq; Christophe Pannecouque; Simon Cocklin; Kuo-Hsiung Lee; Xinyong Liu; Peng Zhan
Journal:  J Med Chem       Date:  2020-04-29       Impact factor: 7.446

5.  Rapid Optimization of the Metabolic Stability of a Human Immunodeficiency Virus Type-1 Capsid Inhibitor Using a Multistep Computational Workflow.

Authors:  Megan E Meuser; Poli Adi Narayana Reddy; Alexej Dick; Jean Marc Maurancy; Joseph M Salvino; Simon Cocklin
Journal:  J Med Chem       Date:  2021-03-22       Impact factor: 7.446

Review 6.  Antibody-Mediated Therapy against HIV/AIDS: Where Are We Standing Now?

Authors:  Noel Jacques Awi; Sin-Yeang Teow
Journal:  J Pathog       Date:  2018-06-03

Review 7.  Recent Advances in HIV-1 Gag Inhibitor Design and Development.

Authors:  Alexej Dick; Simon Cocklin
Journal:  Molecules       Date:  2020-04-07       Impact factor: 4.411

8.  Small-Molecule Anti-HIV-1 Agents Based on HIV-1 Capsid Proteins.

Authors:  Takuya Kobayakawa; Masaru Yokoyama; Kohei Tsuji; Masayuki Fujino; Masaki Kurakami; Sayaka Boku; Miyuki Nakayama; Moemi Kaneko; Nami Ohashi; Osamu Kotani; Tsutomu Murakami; Hironori Sato; Hirokazu Tamamura
Journal:  Biomolecules       Date:  2021-02-03

Review 9.  HIV Capsid Inhibitors Beyond PF74.

Authors:  Carole McArthur; Fabio Gallazzi; Thomas P Quinn; Kamal Singh
Journal:  Diseases       Date:  2019-10-30

10.  Discovery of novel 1,4-disubstituted 1,2,3-triazole phenylalanine derivatives as HIV-1 capsid inhibitors.

Authors:  Xiangyi Jiang; Gaochan Wu; Waleed A Zalloum; Megan E Meuser; Alexej Dick; Lin Sun; Chin-Ho Chen; Dongwei Kang; Lanlan Jing; Ruifang Jia; Simon Cocklin; Kuo-Hsiung Lee; Xinyong Liu; Peng Zhan
Journal:  RSC Adv       Date:  2019-09-16       Impact factor: 4.036
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