Sanchitra, JahanviDebnath, AbhijitSingh, Anil kumarJha, Abhimanyu KumarSingh, Rajesh Kumar2025-07-092025-07-09202520452322https://dl.bhu.ac.in/ir/handle/123456789/111895Hepatitis B Virus (HBV) constitutes a chronic viral infection with limited therapeutic options and a significant global health challenge. The virus lifecycle intricacy significantly relies on the core protein crucial for virus structure stability and interaction with host cells thus contributing to the infection’s persistence and severity. This study employs advanced techniques for the identification of novel core protein inhibitors through the screening of two chemical databases ZINC and BIMP utilizing computational methods such as structure-based virtual screening, drug-likeness, ADME, toxicity, consensus molecular docking, density functional theory, and 100 ns molecular dynamics simulation. The compound ZINC00674395 possesses high affinity and specificity towards core protein demonstrating drug-like properties, favorable ADME profiles, non-toxicity, and favorable electronic configuration with high stability at the core protein active site thus highlighting its potential as a therapeutic agent. These findings offer new insights into core protein interaction and pave the way for developing effective HBV therapeutics. © The Author(s) 2025.Computational drug discoveryConsensus molecular DockingHBV capsid assembly inhibitorsMolecular dynamics simulationStructure-based virtual screeningArticlehttps://doi.org/10.1038/s41598-025-97242-6