Effect of solvation on the molecular structure, vibrational assignment, nature of bonding, and the antiviral drug-like potential of troxerutin against HBV proteins

Abstract

Drugs used in the management of Hepatitis B virus (HBV) infection are largely based on nucleosides or their analogues and these have several side-effects. These drugs only inhibit viral replication, cannot eliminate cccDNA and present with serious long-term effects. Hence, researchers are now searching for potential targets that present with less side-effect and are more effective. The study was aimed at evaluating and comparing the antiviral drug-like potential of troxerutin against various HBV proteins and entecavir. In this study, troxerutin was purified, synthesized and characterized using 1H NMR, 13C NMR and FT-IR. In addition, detailed investigation using density functional theory (DFT), and in-silico molecular docking of troxerutin and entecavir against various HBV proteins were conducted. The spectral analysis (NMR and FT-IR) confirmed the presence of characteristic functional groups with the presence of C–H, C–C and OH bonds/vibrations. Docking result showed excellent binding affinities across all four HBV proteins with the bindings scores for troxerutin (−6.3 to −7.1 kcal/mol) that was similar to those of entecavir (−6.2 to −7.8 kcal/mol). Unlike entecavir, troxerutin did not show any predicted hepatotoxicity but appears to be immunotoxic with an LD50 value of 1000 mg/kg. Given the anti-HBV potential of troxerutin this study has revealed, further in-vivo and in-vitro studies are needed to validate these findings.