ArticleThe Journal of clinical investigation2005
Identification of cellular deoxyhypusine synthase as a novel target for antiretroviral therapy.
Article in The Journal of clinical investigation, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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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
38 citing papers in PubMed, 92 citations in OpenAlex.
- Trial
- eIF5A and hypusination-related disorders: literature review and case report of DOHH-related encephalopathy.Journal of neurodevelopmental disorders · 2025Review
- The Role of Spermidine and Its Key Metabolites in Important, Pathogenic Human Viruses and in Parasitic Infections Caused byBiomolecules · 2023Review
- Bi-allelic variants in DOHH, catalyzing the last step of hypusine biosynthesis, are associated with a neurodevelopmental disorder.American journal of human genetics · 2022Article
- Hypusinated EIF5A as a feasible drug target for Advanced Medicinal Therapies in the treatment of pathogenic parasites and therapy-resistant tumors.Amino acids · 2022Review
- eIF5A is activated by virus infection or dsRNA and facilitates virus replication through modulation of interferon production.Frontiers in cellular and infection microbiology · 2022Article
- The eukaryotic initiation factor 5A (eIF5A1), the molecule, mechanisms and recent insights into the pathophysiological roles.Cell & bioscience · 2021Review
- eIF5A inhibition influences T cell dynamics in the pancreatic microenvironment of the humanized mouse model of Type 1 Diabetes.Scientific reports · 2019Article
- Evolutionary analysis of polyproline motifs in Escherichia coli reveals their regulatory role in translation.PLoS computational biology · 2018Article
- Hypusination of eIF5A as a Target for Antiviral Therapy.DNA and cell biology · 2017Article
- Iron overload down-regulates the expression of the HIV-1 Rev cofactor eIF5A in infected T lymphocytes.Proteome science · 2017Article
- Prognostic significance of the expression of nuclear eukaryotic translation initiation factor 5A2 in human melanoma.Oncology letters · 2016Article
- Repositioning the Old Fungicide Ciclopirox for New Medical Uses.Current pharmaceutical design · 2016Review
- Biological Relevance and Therapeutic Potential of the Hypusine Modification System.The Journal of biological chemistry · 2015Article
- Pokeweed antiviral protein alters splicing of HIV-1 RNAs, resulting in reduced virus production.RNA (New York, N.Y.) · 2014Article
- A novel mouse model for inhibition of DOHH-mediated hypusine modification reveals a crucial function in embryonic development, proliferation and oncogenic transformation.Disease models & mechanisms · 2014Article
- Characterization of a novel polyclonal anti-hypusine antibody.SpringerPlus · 2013Article
- Article
- Evaluation of deoxyhypusine synthase inhibitors targeting BCR-ABL positive leukemias.Investigational new drugs · 2012Article
- In vitro and in vivo silencing of plasmodial dhs and eIf-5a genes in a putative, non-canonical RNAi-related pathway.BMC microbiology · 2012Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The introduction of highly active antiretroviral therapy (HAART) has significantly decreased morbidity and mortality among patients infected with HIV-1. However, HIV-1 can acquire resistance against all currently available antiretroviral drugs targeting viral reverse transcriptase, protease, and gp41. Moreover, in a growing number of patients, the development of multidrug-resistant viruses compromises HAART efficacy and limits therapeutic options. Therefore, it is an ongoing task to develop new drugs and to identify new targets for antiretroviral therapy. Here, we identified the guanylhydrazone CNI-1493 as an efficient inhibitor of human deoxyhypusine synthase (DHS). By inhibiting DHS, this compound suppresses hypusine formation and, thereby, activation of eukaryotic initiation factor 5A (eIF-5A), a cellular cofactor of the HIV-1 Rev regulatory protein. We demonstrate that inhibition of DHS by CNI-1493 or RNA interference efficiently suppressed the retroviral replication cycle in cell culture and primary cells. We show that CNI-1493 inhibits replication of macrophage- and T cell-tropic laboratory strains, clinical isolates, and viral strains with high-level resistance to inhibitors of viral protease and reverse transcriptase. Moreover, no measurable drug-induced adverse effects on cell cycle transition, apoptosis, and general cytotoxicity were observed. Therefore, human DHS represents a novel and promising drug target for the development of advanced antiretroviral therapies, particularly for the inhibition of multidrug-resistant viruses.
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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.