Network Pharmacology and Molecular Docking-Based Approach Investigating Secondary Metabolites from Aquilaria malaccensis as Potential Hepatitis B Agents
Year: 2026
Type: article
Abstract: Chronic hepatitis B (CHB) is one of the significant worldwide health burdens. While existing nucleos(t)ide analogues successfully suppress viral replication, they fail to eradicate the intrahepatic covalently closed circular DNA (cccDNA) reservoir. Persistent infection is also associated with the dysregulation of host signaling pathways involved in metabolism, inflammation, and hepatocarcinogenesis. This study investigates secondary metabolites from Aquilaria malaccensis as potential multi-target compounds acting on host pathways relevant to HBV pathogenesis, with a specific focus on PIK3CA, SRC, and TP53. An integrated in silico approach was applied to 30 phytochemical compounds. Combining drug-likeness assessment, network pharmacology, molecular docking, and 50 ns all-atom molecular dynamics (MD) simulations. Of these, 93.3% satisfied Lipinski’s Rule of Five, indicating physicochemical properties generally favorable for oral drug development. Network pharmacology analysis identified 166 overlapping targets, with PIK3CA, SRC, and TP53 emerging as key hub genes based on network centrality. Molecular docking highlighted 5-hydroxy-6-methoxy-2-(2-phenylethyl)chromone (16), luteolin 7,4′-dimethyl ether (pilloin) (4), and phorbol ester (25) as the most promising compounds, with predicted binding energies reaching -9.8 kcal/mol. During MD simulations, compound 16 exhibited relatively stable interactions within the PIK3CA catalytic cleft (mean RMSD 2.09 Å), luteolin 7,4′-dimethyl ether (pilloin) (4) maintained interactions with the SRC kinase domain (mean RMSD 2.23 Å), and phorbol ester (25) showed low conformational fluctuation within the TP53 DNA-binding domain (mean RMSF 0.75 Å). These findings identify several A. malaccensis metabolites as priority candidates for further research and provide a computational basis for subsequent in vitro and in vivo studies on the potential host-targeting effects of these compounds in the context of CHB.
Language: English
Topic: Wood and Agarwood Research
Subfield: Forestry
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7218719715