A HTRF based competitive binding assay for screening specific inhibitors of HIV-1 capsid assembly targeting the C-Terminal domain of capsid.

Binding, Competitive Capsid / drug effects Capsid Proteins / drug effects Cell Line Drug Evaluation, Preclinical / methods Drug Liberation Fluorescence HIV-1 / drug effects High-Throughput Screening Assays / methods Recombinant Proteins T-Lymphocytes Virus Assembly / drug effects Virus Replication / drug effects
Capsid C-Terminal domain Drug discovery HIV-1 capsid HTRF TX-1918

Journal

Antiviral research
ISSN: 1872-9096
Titre abrégé: Antiviral Res
Pays: Netherlands
ID NLM: 8109699

Informations de publication

Date de publication:
09 2019
Historique:
received: 01 10 2018
revised: 13 06 2019
accepted: 20 06 2019
pubmed: 30 6 2019
medline: 8 7 2020
entrez: 30 6 2019
Statut: ppublish

Résumé

Due to its multifaceted essential roles in virus replication and extreme genetic fragility, the human immunodeficiency virus type 1 (HIV-1) capsid (CA) protein is a valued therapeutic target. However, CA is as yet unexploited clinically, as there are no antiviral agents that target it currently on the market. To facilitate the identification of potential HIV-1 CA inhibitors, we established a homogeneous time-resolved fluorescence (HTRF) assay to screen for small molecules that target a biologically active and specific binding pocket in the C-terminal domain of HIV-1 CA (CA CTD). The assay, which is based on competition of small molecules for the binding of a known CA inhibitor (CAI) to the CA CTD, exhibited a signal-to-background ratio (S/B) > 10 and a Z' value > 0.9. In a pilot screen of three kinase inhibitor libraries containing 464 compounds, we identified one compound, TX-1918, as a low micromolecular inhibitor of the HIV-1 CA CTD-CAI interaction (IC

Identifiants

DOI: 10.1016/j.antiviral.2019.104544 PMID: 31254557 PMC: PMC6901019
pubmed: 31254557
pii: S0166-3542(18)30590-4
doi: 10.1016/j.antiviral.2019.104544
pmc: PMC6901019
mid: NIHMS1060527
pii:
doi:

Substances chimiques

Capsid Proteins 0
Recombinant Proteins 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

104544

Subventions

Organisme : NIAID NIH HHS
ID : P50 AI150481
Pays : United States
Organisme : NIGMS NIH HHS
ID : P50 GM082251
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007386
Pays : United States

Informations de copyright

Copyright © 2019 Elsevier B.V. All rights reserved.

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Auteurs

Da-Wei Zhang (DW)

Institute of Bioinformatics and Medical Engineering, School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou, 213001, China; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA.

Rong-Hua Luo (RH)

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, The National Kunming High Level Biosafety Research Center for Nonhuman Primate, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China.

Lei Xu (L)

Institute of Bioinformatics and Medical Engineering, School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou, 213001, China.

Liu-Meng Yang (LM)

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, The National Kunming High Level Biosafety Research Center for Nonhuman Primate, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China.

Xiao-Shuang Xu (XS)

Institute of Bioinformatics and Medical Engineering, School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou, 213001, China.

Gregory J Bedwell (GJ)

Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA.

Alan N Engelman (AN)

Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA.

Yong-Tang Zheng (YT)

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, The National Kunming High Level Biosafety Research Center for Nonhuman Primate, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China. Electronic address: zhengyt@mail.kiz.ac.cn.

Shan Chang (S)

Institute of Bioinformatics and Medical Engineering, School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou, 213001, China. Electronic address: schang@jsut.edu.cn.

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Classifications MeSH

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questionsmedicales.fr › Structures virales › Virion › Nucléocapside › Capside › A HTRF based competitive binding assay for...
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questionsmedicales.fr › Cellules › Cellules cultivées › Lignée cellulaire › A HTRF based competitive binding assay for...
questionsmedicales.fr › Techniques d'investigation › Évaluation préclinique de médicament › A HTRF based competitive binding assay for...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Pharmacocinétique › Libération de médicament › A HTRF based competitive binding assay for...
questionsmedicales.fr › Phénomènes physiques › Phénomènes optiques › Fluorescence › A HTRF based competitive binding assay for...
questionsmedicales.fr › Virus › Virus à ARN › Retroviridae › Lentivirus › Lentivirus des primates › VIH (Virus de l'Immunodéficience Humaine) › VIH-1 (Virus de l'Immunodéficience Humaine de type 1) › A HTRF based competitive binding assay for...
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questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines recombinantes › A HTRF based competitive binding assay for...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › A HTRF based competitive binding assay for...
questionsmedicales.fr › Phénomènes microbiologiques › Phénomènes physiologiques viraux › Réplication virale › Assemblage viral › A HTRF based competitive binding assay for...
questionsmedicales.fr › Phénomènes microbiologiques › Phénomènes physiologiques viraux › Réplication virale › A HTRF based competitive binding assay for...