ArticleAntimicrobial agents and chemotherapy2015
The bioactive lipid 4-hydroxyphenyl retinamide inhibits flavivirus replication.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 53 citations in OpenAlex.
- Broad-acting antivirals: the pursuit of pan-viral therapeutics in the era of pandemics.Journal of virology · 2026Review
- Dengue virus and lipid metabolism: unravelling the interplay for future therapeutic approaches.Emerging microbes & infections · 2025Review
- A Comprehensive Review of the Development and Therapeutic Use of Antivirals in Flavivirus Infection.Viruses · 2025Review
- Machine learning and molecular docking prediction of potential inhibitors against dengue virus.Frontiers in chemistry · 2024Article
- Increased In Vivo Exposure of N-(4-Hydroxyphenyl) Retinamide (4-HPR) to Achieve Plasma Concentrations Effective against Dengue Virus.Pharmaceutics · 2023Article
- Review
- Review
- A review on structural genomics approach applied for drug discovery against three vector-borne viral diseases: Dengue, Chikungunya and Zika.Virus genes · 2022Review
- Ceramide and Related Molecules in Viral Infections.International journal of molecular sciences · 2021Review
- Antivirals that target the host IMPα/β1-virus interface.Biochemical Society transactions · 2021Review
- Review
- Anti-flavivirus Properties of Lipid-Lowering Drugs.Frontiers in physiology · 2021Review
- Pulmonary Delivery of Fenretinide: A Possible Adjuvant Treatment In COVID-19.International journal of molecular sciences · 2020Review
- Identification of anti-flaviviral drugs with mosquitocidal and anti-Zika virus activity in Aedes aegypti.PLoS neglected tropical diseases · 2019Article
- Fenretinide Inhibits Neutrophil Recruitment and IL-1β Production in Aspergillus fumigatus Keratitis.Cornea · 2018Article
- Characterization and structure-activity relationship analysis of a class of antiviral compounds that directly bind dengue virus capsid protein and are incorporated into virions.Antiviral research · 2018Article
- Dynamic remodeling of lipids coincides with dengue virus replication in the midgut of Aedes aegypti mosquitoes.PLoS pathogens · 2018Article
- Antiviral activity of N-(4-hydroxyphenyl) retinamide (4-HPR) against Zika virus.Antiviral research · 2017Article
- Broad-spectrum agents for flaviviral infections: dengue, Zika and beyond.Nature reviews. Drug discovery · 2017Review
- Structure-Activity Relationship Study of QL47: A Broad-Spectrum Antiviral Agent.ACS medicinal chemistry letters · 2017Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Dengue virus (DENV), a member of the Flaviviridae family, is a mosquito-borne pathogen and the cause of dengue fever. The increasing prevalence of DENV worldwide heightens the need for an effective vaccine and specific antivirals. Due to the dependence of DENV upon the lipid biosynthetic machinery of the host cell, lipid signaling and metabolism present unique opportunities for inhibiting viral replication. We screened a library of bioactive lipids and modulators of lipid metabolism and identified 4-hydroxyphenyl retinamide (4-HPR) (fenretinide) as an inhibitor of DENV in cell culture. 4-HPR inhibits the steady-state accumulation of viral genomic RNA and reduces viremia when orally administered in a murine model of DENV infection. The molecular target responsible for this antiviral activity is distinct from other known inhibitors of DENV but appears to affect other members of the Flaviviridae, including the West Nile, Modoc, and hepatitis C viruses. Although long-chain ceramides have been implicated in DENV replication, we demonstrate that DENV is insensitive to the perturbation of long-chain ceramides in mammalian cell culture and that the effect of 4-HPR on dihydroceramide homeostasis is separable from its antiviral activity. Likewise, the induction of reactive oxygen species by 4-HPR is not required for the inhibition of DENV. The inhibition of DENV in vivo by 4-HPR, combined with its well-established safety and tolerability in humans, suggests that it may be repurposed as a pan-Flaviviridae antiviral agent. This work also illustrates the utility of bioactive lipid screens for identifying critical interactions of DENV and other viral pathogens with host lipid biosynthesis, metabolism, and signal transduction.
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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.