ArticleRetrovirology2009
Inhibition of HIV-1 gene expression by Ciclopirox and Deferiprone, drugs that prevent hypusination of eukaryotic initiation factor 5A.
Article in Retrovirology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 108 citations in OpenAlex.
- Trial
- Brazilin attenuates methylglyoxal‑induced endothelial injury by enhancing eIF5A hypusination and inhibiting the AMPK/mTOR‑mediated autophagy/apoptosis axisInternational journal of molecular medicine · 2026Article
- Ciclopirox reprograms effector responses and modulates Notch1 activation in activated human T cells.iScience · 2026Article
- Polyamines as Gatekeepers of Virus Replication and Central Nervous System Homeostasis.Pathogens (Basel, Switzerland) · 2026Review
- Ciclopirox suppresses poxvirus replication by targeting iron metabolism.Antiviral research · 2025Article
- In Vitro Ciclopirox Glucuronidation in Liver Microsomes from Humans and Various Experimental Animals.European journal of drug metabolism and pharmacokinetics · 2024Article
- Hepatitis C Virus Dysregulates Polyamine and Proline Metabolism and Perturbs the Urea Cycle.Cells · 2024Article
- Ciclopirox inhibits SARS-CoV-2 replication by promoting the degradation of the nucleocapsid protein.Acta pharmaceutica Sinica. B · 2024Article
- Good cop, bad cop: Polyamines play both sides in host immunity and viral replication.Seminars in cell & developmental biology · 2023Review
- The Vital Role Played by Deferiprone in the Transition of Thalassaemia from a Fatal to a Chronic Disease and Challenges in Its Repurposing for Use in Non-Iron-Loaded Diseases.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Polyamines and eIF5A hypusination facilitate SREBP2 synthesis and cholesterol production leading to enhanced enterovirus attachment and infection.PLoS pathogens · 2023Article
- Ciclopirox Inhibition of eIF5A Hypusination Attenuates Fibroblast Activation and Cardiac Fibrosis.Journal of cardiovascular development and disease · 2023Article
- Translation factor accelerating peptide bond formation on the ribosome: EF-P and eIF5A as entropic catalysts and a potential drug targets.BBA advances · 2023Article
- Review
- Deferiprone: A Forty-Year-Old Multi-Targeting Drug with Possible Activity against COVID-19 and Diseases of Similar Symptomatology.International journal of molecular sciences · 2022Review
- HIV-1 infection in sickle cell disease and sickle cell trait: role of iron and innate response.Expert review of hematology · 2022Article
- eIF5A is activated by virus infection or dsRNA and facilitates virus replication through modulation of interferon production.Frontiers in cellular and infection microbiology · 2022Article
- Bracovirus Sneaks Into Apoptotic Bodies Transmitting Immunosuppressive Signaling Driven by Integration-Mediated eIF5A Hypusination.Frontiers in immunology · 2022Article
- The eukaryotic initiation factor 5A (eIF5A1), the molecule, mechanisms and recent insights into the pathophysiological roles.Cell & bioscience · 2021Review
- Intracellular Low Iron Exerts Anti-BK Polyomavirus Effect by Inhibiting the Protein Synthesis of Exogenous Genes.Microbiology spectrum · 2021Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundEukaryotic translation initiation factor eIF5A has been implicated in HIV-1 replication. This protein contains the apparently unique amino acid hypusine that is formed by the post-translational modification of a lysine residue catalyzed by deoxyhypusine synthase and deoxyhypusine hydroxylase (DOHH). DOHH activity is inhibited by two clinically used drugs, the topical fungicide ciclopirox and the systemic medicinal iron chelator deferiprone. Deferiprone has been reported to inhibit HIV-1 replication in tissue culture.
resultsCiclopirox and deferiprone blocked HIV-1 replication in PBMCs. To examine the underlying mechanisms, we investigated the action of the drugs on eIF5A modification and HIV-1 gene expression in model systems. At early times after drug exposure, both drugs inhibited substrate binding to DOHH and prevented the formation of mature eIF5A. Viral gene expression from HIV-1 molecular clones was suppressed at the RNA level independently of all viral genes. The inhibition was specific for the viral promoter and occurred at the level of HIV-1 transcription initiation. Partial knockdown of eIF5A-1 by siRNA led to inhibition of HIV-1 gene expression that was non-additive with drug action. These data support the importance of eIF5A and hypusine formation in HIV-1 gene expression.
conclusionAt clinically relevant concentrations, two widely used drugs blocked HIV-1 replication ex vivo. They specifically inhibited expression from the HIV-1 promoter at the level of transcription initiation. Both drugs interfered with the hydroxylation step in the hypusine modification of eIF5A. These results have profound implications for the potential therapeutic use of these drugs as antiretrovirals and for the development of optimized analogs.
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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.