In silico-based Exploration of Moringa oleifera Phytochemicals as Potential Inhibitors of the Hepatitis B Virus X Protein

Abstract

Background: Hepatitis B virus (HBV) infection remains a major global health concern. The HBV X protein (HBx) plays an important role in viral gene regulation and replication and represents a potential molecular target for antiviral compound screening. Aim: This study evaluated the predicted interactions of selected Moringa oleifera phytochemicals with HBx using in silico approaches. Materials and Methods: Five M. oleifera phytochemicals (quercetin, rutin, chlorogenic acid, gallic acid, and moringin) and gambogic acid, used as a reference compound, were evaluated against HBx. Toxicity profiles were predicted using ProTox-II, while molecular docking was performed using PyRx. Protein–ligand interactions were subsequently analyzed using BIOVIA Discovery Studio. Results: All six compounds were predicted to be inactive for hepatotoxicity. Rutin, chlorogenic acid, moringin and gambogic acid were predicted to be inactive across all assessed toxicity endpoints. These compounds also showed favourable predicted binding affinities in PyRx, with interactions involving key HBx residues, including Leu93, Pro90 and Thr97. Rutin, chlorogenic acid, and quercetin exhibited particularly favourable predicted interactions with the HBx binding site. Conclusion: The in silico analysis identified several M. oleifera phytochemicals with favourable predicted toxicity profiles and interactions with HBx, particularly rutin, chlorogenic acid, and quercetin. These findings suggest that these compounds may interact with HBx and potentially modulate HBx-associated molecular processes. However, experimental studies are required to validate these computational predictions and determine their biological relevance.