ArticleFrontiers in pharmacology2012
Bilirubin: An Endogenous Molecule with Antiviral Activity in vitro.
Article in Frontiers in pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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.
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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
22 citing papers in PubMed, 34 citations in OpenAlex.
- Therapeutic Gases in Biomedicine: Updates on Nitric Oxide and Beyond.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- The Heme Oxygenase/Biliverdin Reductase System and Its Genetic Variants in Physiology and Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- The Role of the Nrf2 Pathway in Airway Tissue Damage Due to Viral Respiratory Infections.International journal of molecular sciences · 2024Review
- COVID-19 and β-thalassemia: in lieu of evidence and vague nexus.Annals of hematology · 2024Review
- Heme oxygenase-1 is an equid alphaherpesvirus 8 replication restriction host protein and suppresses viral replication via the PKCβ/ERK1/ERK2 and NO/cGMP/PKG pathway.Microbiology spectrum · 2024Article
- The Role of the NRF2 Pathway in the Pathogenesis of Viral Respiratory Infections.Pathogens (Basel, Switzerland) · 2023Review
- NO in Viral Infections: Role and Development of Antiviral Therapies.Molecules (Basel, Switzerland) · 2022Review
- Induction of HOXA3 by Porcine Reproductive and Respiratory Syndrome Virus Inhibits Type I Interferon Response through Negative Regulation of HO-1 Transcription.Journal of virology · 2022Article
- A new parameter for predict the clinical outcome of patients with COVID-19 pneumonia: The direct/total bilirubin ratio.International journal of clinical practice · 2021Article
- Can bilirubin nanomedicine become a hope for the management of COVID-19?Medical hypotheses · 2021Article
- Nitric oxide and viral infection: Recent developments in antiviral therapies and platforms.Applied materials today · 2021Review
- Case Report: Hyperbilirubinemia in Gilbert Syndrome Attenuates Covid-19-Induced Metabolic Disturbances.Frontiers in cardiovascular medicine · 2021Article
- Isolation and Identification ofFrontiers in pharmacology · 2021Article
- Heme oxygenase-1 modulation: A potential therapeutic target for COVID-19 and associated complications.Free radical biology & medicine · 2020Review
- Heme oxygenase-1 in protozoan infections: A tale of resistance and disease tolerance.PLoS pathogens · 2020Review
- Targeting the Heme-Heme Oxygenase System to Prevent Severe Complications Following COVID-19 Infections.Antioxidants (Basel, Switzerland) · 2020Article
- The Cytoprotective Enzyme Heme Oxygenase-1 Suppresses Pseudorabies Virus ReplicationFrontiers in microbiology · 2020Article
- Heme-Derived Metabolic Signals Dictate Immune Responses.Frontiers in immunology · 2020Review
- Curcumin, Hormesis and the Nervous System.Nutrients · 2019Review
- Curcumin and Heme Oxygenase: Neuroprotection and Beyond.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bilirubin-IX-alpha (BR) is the final product of heme metabolism through the heme oxygenase/biliverdin reductase (HO/BVR) system. Previous papers reported on the microbicidal effects of the HO by-products biliverdin-IX-alpha, carbon monoxide and iron, through either direct or indirect mechanisms. In this paper the evidence of a virucidal effect of BR against human herpes simplex virus type 1 (HSV-1) and the enterovirus EV71 was provided. Bilirubin-IX-alpha, at concentrations 1-10 μM, close to those found in blood and tissues, significantly reduced HSV-1 and EV71 replication in Hep-2 and Vero cell lines, respectively. Bilirubin-IX-alpha inhibited viral infection of Hep-2 and Vero cells when given 2 h before, concomitantly and 2 h after viral infection. Furthermore, BR retained its antiviral activity even complexed with a saturating concentration of human serum-albumin. Moreover, 10 μM BR increased the formation of nitric oxide and the phosphorylation of c-Jun N-terminal kinase in Vero and Hep-2 cell lines, respectively, thus implying a role of these two pathways in the mechanism of antiviral activity of the bile pigment. In conclusion, these results support the antiviral effect of BR against HSV-1 and enterovirus in vitro, and put the basis for further basic and clinical studies to understand the real role of BR as an endogenous antiviral molecule.
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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.