ArticlePloS one2018
Rosmarinic acid is a novel inhibitor for Hepatitis B virus replication targeting viral epsilon RNA-polymerase interaction.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 59 citations in OpenAlex.
- Antibacterial Activity of Rosmarinic Acid AgainstAnimals : an open access journal from MDPI · 2026Article
- West African Medicinal Plant Substances and Molecules Activities Against Viral Hepatitis B and Hepatocellular Carcinoma.Recent patents on anti-cancer drug discovery · 2026Review
- The Antiviral Activity of Polyphenols.Molecular nutrition & food research · 2025Review
- The Evolution of Cell Culture Systems to Study Hepatitis B Virus Pathogenesis and Antiviral Susceptibility.Viruses · 2025Review
- Evaluating the Antiviral Potential of Polyherbal Formulation (Life (Basel, Switzerland) · 2025Article
- Review
- Rosmarinic Acid inhibits Pseudorabies Virus (PRV) infection by activating the cGAS-STING signaling pathway.BMC microbiology · 2025Article
- Article
- Exploration of the in vitro Antiviral Effects and the Active Components of Changyanning Tablets Against Enterovirus 71.Drug design, development and therapy · 2024Article
- Unlocking the antiviral potential of rosmarinic acid against chikungunya virus via IL-17 signaling pathway.Frontiers in cellular and infection microbiology · 2024Article
- An overview of anti-Hepatitis B virus flavonoids and their mechanisms of action.Frontiers in cellular and infection microbiology · 2024Review
- Metabolites from traditional Chinese botanical drugs with anti-hepatitis B virus activity - a review.Frontiers in pharmacology · 2024Review
- Hepatitis B Virus Epsilon (ε) RNA Element: Dynamic Regulator of Viral Replication and Attractive Therapeutic Target.Viruses · 2023Review
- Application of Rosmarinic Acid with Its Derivatives in the Treatment of Microbial Pathogens.Molecules (Basel, Switzerland) · 2023Review
- Phenolic Content, Antioxidant, Antibacterial, Antihyperglycemic, and α-Amylase Inhibitory Activities of Aqueous Extract ofPharmaceuticals (Basel, Switzerland) · 2023Article
- (Revista brasileira de farmacognosia : orgao oficial da Sociedade Brasileira de Farmacognosia · 2023Article
- Journey of Rosmarinic Acid as Biomedicine to Nano-Biomedicine for Treating Cancer: Current Strategies and Future Perspectives.Pharmaceutics · 2022Review
- A Comprehensive Review of Rosmarinic Acid: From Phytochemistry to Pharmacology and Its New Insight.Molecules (Basel, Switzerland) · 2022Review
- In Silico and In Vitro Identification of Pan-Coronaviral Main Protease Inhibitors from a Large Natural Product Library.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Ellagic Acid as a Potential Inhibitor against the Nonstructural Protein NS3 Helicase of Zika Virus: A Molecular Modelling Study.BioMed research international · 2022Article
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Current therapeutics for hepatitis B virus (HBV) patients such as nucleoside analogs (NAs) are effective; however, new antiviral drugs against HBV are still desired. Since the interaction between the epsilon (ε) sequence of HBV pregenomic RNA and viral polymerase (Pol) is a key step in the HBV replication cycle, we aimed to identify small compounds for its inhibition, and established a pull-down assay system for the detection of ε-RNA-binding-Pol. Screening showed that 5 out of 3,965 compounds inhibited ε-Pol binding, and we identified rosmarinic acid, which exhibited specificity, as a potential antiviral agent. In order to examine the anti-HBV effects of rosmarinic acid, HBV-infected primary human hepatocytes from a humanized mouse liver were treated with rosmarinic acid. The rosmarinic acid treatment decreased HBV components including the amounts of extracellular HBV DNA with negligible cytotoxicity. We also investigated the combined effects of rosmarinic acid and the NA, lamivudine. rosmarinic acid slightly enhanced the anti-HBV activity of lamivudine, suggesting that the HBV replication step targeted by rosmarinic acid is distinct from that of NA. We analyzed an additional 25 rosmarinic acid derivatives, and found that 5 also inhibited ε-Pol. Structural comparisons between these derivatives implied that the "two phenolic hydroxyl groups at both ends" and the "caffeic acid-like structure" of rosmarinic acid are critical for the inhibition of ε-Pol binding. Collectively, our results demonstrate that rosmarinic acid inhibits HBV replication in HBV-infected cells by specifically targeting ε-Pol binding.
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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.