ArticleACS chemical biology2009
Chemical library screens targeting an HIV-1 accessory factor/host cell kinase complex identify novel antiretroviral compounds.
Article in ACS chemical biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 67 citations in OpenAlex.
- Structure-Activity Relationships of Natural and Semisynthetic Plecomacrolides Suggest Distinct Pathways for HIV-1 Immune Evasion and Vacuolar ATPase-Dependent Lysosomal Acidification.Journal of medicinal chemistry · 2024Article
- Review
- Neutron Reflectometry and Molecular Simulations Demonstrate HIV-1 Nef Homodimer Formation on Model Lipid Bilayers.Journal of molecular biology · 2023Article
- The HIV-1 protein Nef activates the Tec family kinase Btk by stabilizing an intermolecular SH3-SH2 domain interaction.Science signaling · 2022Article
- Review
- Inhibitors of HIV-1 Nef-Mediated Activation of the Myeloid Src-Family Kinase Hck Block HIV-1 Replication in Macrophages and Disrupt MHC-I Downregulation.ACS infectious diseases · 2022Article
- The BLT Humanized Mouse Model as a Tool for Studying Human Gamma Delta T Cell-HIV InteractionsFrontiers in immunology · 2022Article
- Visualization of Host Cell Kinase Activation by Viral Proteins Using GFP Fluorescence Complementation and Immunofluorescence Microscopy.Bio-protocol · 2021Article
- Direct interaction between ABCA1 and HIV-1 Nef: Molecular modeling and virtual screening for inhibitors.Computational and structural biotechnology journal · 2021Article
- Nef homodimers down-regulate SERINC5 by AP-2-mediated endocytosis to promote HIV-1 infectivity.The Journal of biological chemistry · 2020Article
- Structure, function, and inhibitor targeting of HIV-1 Nef-effector kinase complexes.The Journal of biological chemistry · 2020Review
- The Dynamic Interface of Viruses with STATs.Journal of virology · 2020Review
- HIV-1 Nef dimers short-circuit immune receptor signaling by activating Tec-family kinases at the host cell membrane.The Journal of biological chemistry · 2020Article
- Tight-Binding Hydroxypyrazole HIV-1 Nef Inhibitors Suppress Viral Replication in Donor Mononuclear Cells and Reverse Nef-Mediated MHC-I Downregulation.ACS infectious diseases · 2020Article
- Discovery of Non-peptide Small Molecule Allosteric Modulators of the Src-family Kinase, Hck.Frontiers in chemistry · 2019Article
- Lovastatin Inhibits HIV-1-Induced MHC-I Downregulation by Targeting Nef-AP-1 Complex Formation: A New Strategy to Boost Immune Eradication of HIV-1 Infected Cells.Frontiers in immunology · 2019Article
- Remodeling of HIV-1 Nef Structure by Src-Family Kinase Binding.Journal of molecular biology · 2018Article
- A single β-octyl glucoside molecule induces HIV-1 Nef dimer formation in the absence of partner protein binding.PloS one · 2018Article
- HIV-I Nef inhibitors: a novel class of HIV-specific immune adjuvants in support of a cure.AIDS research and therapy · 2017Review
- Dynamics of the Tec-family tyrosine kinase SH3 domains.Protein science : a publication of the Protein Society · 2016Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Nef is an HIV-1 accessory protein essential for AIDS progression and an attractive target for drug discovery. Lack of a catalytic function makes Nef difficult to assay in chemical library screens. We developed a high-throughput screening assay for inhibitors of Nef function by coupling it to one of its host cell binding partners, the Src-family kinase Hck. Hck activation is dependent upon Nef in this assay, providing a direct readout of Nef activity in vitro. Using this screen, a unique diphenylfuropyrimidine was identified as a strong inhibitor of Nef-dependent Hck activation. This compound also exhibited remarkable antiretroviral effects, blocking Nef-dependent HIV replication in cell culture. Structurally related analogs were synthesized and shown to exhibit similar Nef-dependent antiviral activity, identifying the diphenylfuropyrimidine substructure as a new lead for antiretroviral drug development. This study demonstrates that coupling noncatalytic HIV accessory factors with host cell target proteins addressable by high-throughput assays may afford new avenues for the discovery of anti-HIV agents.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.