Acta informatica medica : AIM : journal of the Society for Medical Informatics of Bosnia & Herzegovina : casopis Drustva za medicinsku informatiku BiH · 2025
In Silico Screening of Secondary Metabolites from Scorodocarpus Borneensis as Hepatitis B Virus Inhibitors.
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Darmadi Darmadi, Halim Sahat, Lubis Inke Nadia Diniyanti
Аннотация
BACKGROUND: The Hepatitis B Virus (HBV) is a major global health concern, primarily due to its potential to cause chronic liver disease and cancer. The HBV core protein (HBc) is essential for the viral life cycle, specifically in the assembly of the viral capsid, making it a prime target for antiviral drug development. Scorodocarpus borneensis, a plant native to Southeast Asia, is rich in diverse phytochemicals but its potential as a source for antiviral agents against HBV remains largely unexplored.
OBJECTIVE: This study aimed to identify and evaluate secondary metabolites from S. borneensis as potential inhibitors of the HBV core protein through a comprehensive in silico screening and analysis pipeline.
METHODS: Thirty-two compounds derived from S. borneensis were computationally evaluated. The process began with drug-likeness screening based on Lipinski's Rule of Five and initial toxicity predictions. Compounds that passed this filter were then subjected to molecular docking studies against the active site of the HBV core protein (PDB ID: 6J10) to determine their binding affinities and interaction modes. The most promising candidates were selected for in-depth ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis and 20 ns molecular dynamics (MD) simulations to assess the stability of the protein-ligand complexes.
RESULTS: From the initial screening, 17 of the 32 compounds successfully met Lipinski's criteria and showed no significant toxicity. The molecular docking analysis identified three compounds-Scodopin (12), Cadalen-15-oic acid (13), and Icariside B (15)-as the strongest candidates due to their low binding affinities and their occupation of the same active site as the native ligand. Subsequent ADMET prediction highlighted compound 13 for its favorable safety and bioavailability profile. The MD simulation further confirmed that the complex formed between the HBV protein and compound 13 was highly stable, whereas the complexes with compounds 12 and 15 were not.
CONCLUSION: The combined results from drug-likeness prediction, molecular docking, ADMET analysis, and molecular dynamics simulations strongly suggest that Cadalen-15-oic acid (13) is a highly promising lead compound from S. borneensis for developing a novel drug to inhibit the HBV core protein.
OBJECTIVE: This study aimed to identify and evaluate secondary metabolites from S. borneensis as potential inhibitors of the HBV core protein through a comprehensive in silico screening and analysis pipeline.
METHODS: Thirty-two compounds derived from S. borneensis were computationally evaluated. The process began with drug-likeness screening based on Lipinski's Rule of Five and initial toxicity predictions. Compounds that passed this filter were then subjected to molecular docking studies against the active site of the HBV core protein (PDB ID: 6J10) to determine their binding affinities and interaction modes. The most promising candidates were selected for in-depth ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis and 20 ns molecular dynamics (MD) simulations to assess the stability of the protein-ligand complexes.
RESULTS: From the initial screening, 17 of the 32 compounds successfully met Lipinski's criteria and showed no significant toxicity. The molecular docking analysis identified three compounds-Scodopin (12), Cadalen-15-oic acid (13), and Icariside B (15)-as the strongest candidates due to their low binding affinities and their occupation of the same active site as the native ligand. Subsequent ADMET prediction highlighted compound 13 for its favorable safety and bioavailability profile. The MD simulation further confirmed that the complex formed between the HBV protein and compound 13 was highly stable, whereas the complexes with compounds 12 and 15 were not.
CONCLUSION: The combined results from drug-likeness prediction, molecular docking, ADMET analysis, and molecular dynamics simulations strongly suggest that Cadalen-15-oic acid (13) is a highly promising lead compound from S. borneensis for developing a novel drug to inhibit the HBV core protein.