Pharmacoinformatics Analysis Reveal Flavonoids and Diterpenoids from Andrographis Paniculata and Thespesia Populnea as Potential Modulators of Hepatitis B Virus Induced Hepatocellular Carcinoma

Abstract

Herbs are widely utilized in the Western Ghats region of India to treat liver diseases and viral infections. However, such practices lack scientific evidence at the molecular level and may often pose adverse drug reactions. Thus, by this study we intend to identify phytocompounds having druggability and non-toxic profiles with potential activity against HBV-induced HCC. To startwith, the details of phytocompounds in traditionally utilized herbs in Western Ghats region were collated from chemical databases and publications. The druggability and toxicity of these compounds were predicted using MolSoft and ADVERpred, respectively. The probable targets of these phytocompounds were predicted using BindingDB. Moreover, compound-gene set pathways, cellular processes, and functional enrichment analysis were also performed using STRING and KEGG pathway databases. Subsequently, Herb-compound-target-disease pathway networks were constructed using Cytoscape 3.6.1. The potential hub protein was virtually screened against ligand dataset using POAP pipeline. Finally, molecular dynamics (MD) simulations of the most potential protein-ligand complexes were performed in triplicate using Desmond 6.1v. Amongst 274 compounds from 16 herbs studied, 36 showed drug likeness with nontoxic properties, and were also predicted to modulate 16 potential targets involved in the pathogenesis of HBV-induced HCC. Among all the molecules screened, flavonoids and diterpenoids from Andrographis paniculata and Thespesia populnea scored the highest edge count via modulating multiple targets and pathways. Moreover, molecular docking and MD simulation (100ns) also inferred that the top ranking Andrographin and Gossypetin to exhibit stable intermolecular interactions with EGFR protein, which was identified as highly connected hub protein in the constructed network. All these findings are suggestive of these moieties as potential therapeutics for targeting HBV-associated HCC sans adverse drug reactions.