ArticleThe Journal of biological chemistry2010
Gyrase B inhibitor impairs HIV-1 replication by targeting Hsp90 and the capsid protein.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Multiple Inhibitory Factors Act in the Late Phase of HIV-1 Replication: a Systematic Review of the Literature.Microbiology and molecular biology reviews : MMBR · 2018Pooled it
- Heat shock protein 90 is a chaperone regulator of HIV-1 latency.PLoS pathogens · 2025Article
- Geldanamycin, a Naturally Occurring Inhibitor of Hsp90 and a Lead Compound for Medicinal Chemistry.Journal of medicinal chemistry · 2024Review
- The capsid revolution.Journal of molecular cell biology · 2024Review
- HIV-1 capsid and viral DNA integration.mBio · 2024Review
- Emerging role of cyclophilin A in HIV-1 infection: from producer cell to the target cell nucleus.Journal of virology · 2023Review
- A Broad-Spectrum Antiviral Molecule, Protoporphyrin IX, Acts as a Moderator of HIV-1 Capsid Assembly by Targeting the Capsid Hexamer.Microbiology spectrum · 2023Article
- p17-Modulated Hsp90/Cdc37 Complex Governs Oncolytic Avian Reovirus Replication by Chaperoning p17, Which Promotes Viral Protein Synthesis and Accumulation of Viral Proteins σC and σA in Viral Factories.Journal of virology · 2022Article
- Cure and Long-Term Remission Strategies.Methods in molecular biology (Clifton, N.J.) · 2022Review
- Evolving Strategies to Eliminate the CD4 T Cells HIV Viral ReservoirFrontiers in immunology · 2022Review
- Rotten to the core: antivirals targeting the HIV-1 capsid core.Retrovirology · 2021Review
- Th17 cell master transcription factor RORC2 regulates HIV-1 gene expression and viral outgrowth.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- HIV-1 capsid variability: viral exploitation and evasion of capsid-binding molecules.Retrovirology · 2021Review
- Diversity in heat shock protein families: functional implications in virus infection with a comprehensive insight of their role in the HIV-1 life cycle.Cell stress & chaperones · 2021Review
- The Role of Capsid in the Early Steps of HIV-1 Infection: New Insights into the Core of the Matter.Viruses · 2021Review
- Identification of an Antiretroviral Small Molecule That Appears To Be a Host-Targeting Inhibitor of HIV-1 Assembly.Journal of virology · 2021Article
- Block-And-Lock: New Horizons for a Cure for HIV-1.Viruses · 2020Review
- NKNK: a New Essential Motif in the C-Terminal Domain of HIV-1 Group M Integrases.Journal of virology · 2020Article
- HIV-1 Maturation: Lessons Learned from Inhibitors.Viruses · 2020Review
- HSF1 Activation Can Restrict HIV Replication.ACS infectious diseases · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Chemical genetics is an emerging approach to investigate the biology of host-pathogen interactions. We screened several inhibitors of ATP-dependent DNA motors and detected the gyrase B inhibitor coumermycin A1 (C-A1) as a potent antiretroviral. C-A1 inhibited HIV-1 integration and gene expression from acutely infected cell, but the two activities mapped to distinct targets. Target discovery identified Hsp90 as the C-A1 target affecting viral gene expression. Chromatin immunoprecipitation revealed that Hsp90 associates with the viral promoter and may directly regulate gene expression. Molecular docking suggested that C-A1 binds to two novel pockets at the C terminal domain of Hsp90. C-A1 inhibited Hsp90 dimer formation, suggesting that it impairs viral gene expression by preventing Hsp90 dimerization at the C terminus. The inhibition of HIV-1 integration imposed by C-A1 was independent of Hsp90 and mapped to the capsid protein, and a point mutation at residue 105 made the virus resistant to this block. HIV-1 susceptibility to the integration block mediated by C-A1 was influenced by cyclophilin A. Our chemical genetic approach revealed an unexpected function of capsid in HIV-1 integration and provided evidence for a role of Hsp90 in regulating gene expression in mammalian cells. Both activities were amenable to inhibition by small molecules and represent novel antiretroviral drug targets.
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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.