Network Pharmacology-Based Prediction of the Mechanism of Anti-Hepatitis C Virus of Kleinhovia Hospita L

Abstract

Kleinhovia hospita L. is tropical herbaceous plant typically used as traditional medicine, but its potential as an antiviral agent remains scientifically underexplored. Given the limitations of the current hepatitis C virus (HCV) treatments, there is a need to identify novel therapeutic compounds from natural resources. Therefore, this study aims to explore the potential of the methanol extract of Kleinhovia hospita L to treat HCV. Chemical composition of the methanol extract was assessed using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). The protein targets and signaling pathways in HCV due to Kleinhovia hospita L were evaluated with network pharmacology. Computational results were then validated using in vitro testing against HCV. The LC-HRMS analysis results showed that there were 57 compounds in the methanol extract, with 38 complying with drug-likeness properties. Network pharmacology analysis using the 38 compounds showed 331 potential therapeutic targets, with TP53, AKT1, SRC, HSP90AA1, EGFR, GAPDH, and ESR1 serving as core targets. Molecular docking of the best 4 targets (TP53, AKT1, SRC, HSP90AA1) showed that the AKT1-bound docked poses of Compounds 2, 7, 11, 20, 24, 33, 38, 43, and 45 had lower binding energies than native ligand. Meanwhile, compounds 28 and 40 showed lower binding energies than the native ligand when bound to SRC. Lower binding energies were also observed in the HSP90-docked poses of compounds 7, 24, 25, and 55. In vitro test against HCV by the methanol extract showed inhibitory concentration 50 (IC50) of 2.24±0.1 µg/mL, which indicated its potential for inhibiting HCV.