Speakers - 2027

Title: Exploring fascinating potential: Repurposing embelin derivatives for dengue treatment

Abstract

Dengue remains a major global health burden, with the World Health Organization reporting a ten-fold increase in cases from 500,000 in 2000 to 5.2 million in 2019, and over 4.5 million cases and 3,000 deaths recorded since early 2025. Despite its rising incidence and risk of severe disease, effective antiviral therapies are still lacking. Dengvaxia, the first FDA-approved dengue vaccine available in 20 countries for ages 9 to 45, has only 56% efficacy and was withdrawn in the Philippines due to adverse effects on children. Although Takeda’s QDenga vaccine, approved in the EU, offers hope by being effective, research remains critical. Preliminary research suggests that embelin possess potential antiviral effects. However, the potential of embelin in the fight against dengue has not been explored. This study aimed to identify potential anti-dengue agents through the design and evaluation of embelin-derived compounds targeting key viral proteins. A library of 370 repurposed drugs was screened against major dengue targets, including the Envelope protein, NS2BNS3 protease, NS3 helicase, NS5 RNA-dependent RNA polymerase, and NS5 methyltransferase. Molecular docking using AutoDock Vina 1.5.6 identified compounds with multi-target binding potential, followed by ADMET analysis to evaluate pharmacokinetic and toxicity profiles, and molecular dynamics simulations to assess protein–ligand complex stability. Seven repurposed compounds demonstrated strong binding affinities across all selected targets, with consistent hydrogen bonding and aromatic interactions contributing to stable binding. ADMET profiling suggested acceptable pharmacokinetic properties and manageable toxicity risks, while MD simulations confirmed stable interactions throughout the simulation period. These results guided the optimization of embelin-based derivatives with promising antiviral potential. Overall, this study highlights embelin-derived compounds as potential multi-target dengue inhibitors and provides a computational framework integrating docking, ADMET prediction, and molecular dynamics to support future experimental validation through synthesis, cytotoxicity testing, anti-dengue assays, and qRT-PCR analysis.

What will the audience take away from your presentation:

• A validated computational workflow integrating molecular docking, ADMET prediction, and molecular dynamics simulations for prioritizing antiviral drug candidates before experimental testing.
• Identification of seven promising multi-target lead compounds with favourable binding affinities against five essential dengue viral proteins, demonstrating the advantages of multi-target antiviral design.
• Insights into the structural features of embelin-derived compounds that contribute to strong and stable protein–ligand interactions, providing guidance for future compound optimization.
• Evidence-based strategies for reducing time, cost, and failure rates in early-stage antiviral drug discovery by using in silico methods to prioritize compounds for synthesis and biological evaluation.
• A translational roadmap showing how computational findings can be advanced into synthesis, cytotoxicity studies, antiviral assays, and qRT-PCR validation, bridging computational and experimental research.