ArticleMicrobial cell factories2014
The myxobacterial metabolite ratjadone A inhibits HIV infection by blocking the Rev/CRM1-mediated nuclear export pathway.
Article in Microbial cell factories, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Covalent warhead assembly in fostriecin biosynthesis involves malonylation-lactonisation by a bifunctional thioesterase and enzymatic demalonylation.Nature communications · 2026Article
- Genetic engineering of Sorangium cellulosum reveals hidden enzymology in myxobacterial natural product biosynthesis.Nature communications · 2025Article
- The Nucleolus and Its Interactions with Viral Proteins Required for Successful Infection.Cells · 2024Review
- Article
- Therapeutic Targeting of Exportin-1 in Childhood Cancer.Cancers · 2021Review
- Therapeutic applications and biological activities of bacterial bioactive extracts.Archives of microbiology · 2021Review
- Myxobacteria as a Source of New Bioactive Compounds: A Perspective Study.Pharmaceutics · 2021Review
- Myxobacteria and their products: current trends and future perspectives in industrial applications.Folia microbiologica · 2021Review
- Cellular and Viral Determinants of HSV-1 Entry and Intracellular Transport towards Nucleus of Infected Cells.Journal of virology · 2021Article
- The nuclear export protein XPO1 - from biology to targeted therapy.Nature reviews. Clinical oncology · 2021Review
- New Insights into the Link between Melanoma and Thyroid Cancer: Role of Nucleocytoplasmic Trafficking.Cells · 2021Review
- Targeting XPO1 enhances innate immune response and inhibits KSHV lytic replication during primary infection by nuclear stabilization of the p62 autophagy adaptor protein.Cell death & disease · 2021Article
- Anti-allergic drug azelastine suppresses colon tumorigenesis by directly targeting ARF1 to inhibit IQGAP1-ERK-Drp1-mediated mitochondrial fission.Theranostics · 2021Article
- A New Strategy for the Rapid Identification and Validation of the Direct Targets of Aconitine-Induced Cardiotoxicity.Drug design, development and therapy · 2021Article
- Emerging Therapeutic Modalities against COVID-19.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Particulate matter induces inflammatory cytokine production via activation of NFκB by TLR5-NOX4-ROS signaling in human skin keratinocyte and mouse skin.Redox biology · 2019Article
- Review
- Antiviral Compounds from Myxobacteria.Microorganisms · 2018Review
- Does Size Really Matter? Probing the Efficacy of Structural Reduction in the Optimization of Bioderived Compounds - A Computational "Proof-of-Concept".Computational and structural biotechnology journal · 2018Article
- CRM1 Inhibitors for Antiviral Therapy.Frontiers in microbiology · 2017Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe nuclear export of unspliced and partially spliced HIV-1 mRNA is mediated by the recognition of a leucine-rich nuclear export signal (NES) in the HIV Rev protein by the host protein CRM1/Exportin1. This makes the CRM1-Rev complex an attractive target for the development of new antiviral drugs. Here we tested the anti-HIV efficacy of ratjadone A, a CRM1 inhibitor derived from myxobacteria.
resultsRatjadone A inhibits HIV infection in vitro in a dose-dependent manner with EC₅₀ values at the nanomolar range. The inhibitory effect of ratjadone A occurs around 12 hours post-infection and is specific for the Rev/CRM1-mediated nuclear export pathway. By using a drug affinity responsive target stability (DARTS) assay we could demonstrate that ratjadone A interferes with the formation of the CRM1-Rev-NES complex by binding to CRM1 but not to Rev.
conclusionRatjadone A exhibits strong anti-HIV activity but low selectivity due to toxic effects. Although this limits its potential use as a therapeutic drug, further studies with derivatives of ratjadones might help to overcome these difficulties in the future.
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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.