In- silico evaluation of bioactive compounds from selected medicinal plants from Southern Nigeria against hepatitis C virus genotype 1 RNA-directed RNA polymerase

Abstract

BackgroundAt the moment, there is no vaccine for the hepatitis C virus (HCV), despite it being more infectious than the hepatitis B virus (HBV) and the human immunodeficiency virus (HIV). Existing drugs based on protease and polymerase inhibitors present adverse clinical outcomes, sparking the search for alternatives. Medicinal plants contain bioactive compounds that hold great promise. Thus, the present study was aimed at evaluating the druggability of bioactive compounds implicated in folk medicine in the management of HCV against RNA-directed RNA polymerase (RdRp). MethodsTraditional healers involved in the management of hepatitis were consulted, and they suggested the use of leaves of Vernonia amygdalina, Jatropha tanjorensis, Annona muricata, and Solanum nigrum (berries too) in the management of hepatitis. The collection of plant parts and phytochemical screening via gas chromatography-mass spectrophotometer (GC–MS) were carried out. Resulting bioactive compounds and a control HCV drug, remdesivir, were screened for ADMET properties using the pkCSM online prediction tool, while molecular docking was performed using AutoDockTool 1.5.6 and the resulting interactions visualised in 2-Dimension using Discovery Studio 2022 Client. ResultsGC–MS analysis of the medicinal plants revealed 60 bioactive compounds, of which 15 did not violate Lipinski's rule of five and 2 returned only one violation, while the control drug returned two violations. All the ligands were not inhibitors of CYP1A2, CYP2C19, CYPCC9, CYPAD6, and CYP3A4, except for 1,3-dihydrobenzo-[c]thiophen, docosahexaenoic acid, and benzonitrile N-oxide, which were inhibitors of CYP1A2. The intestinal absorption rates of the various ligands (73.56–100 %) were better than those of remdesivir, with an intestinal absorption rate of 67.15 %. Docking analysis revealed scores that ranged from -4.3 to -8.0 k/cal for the ligands, while the score for remdesivir was -9.0 k/cal. Eight ligands and remdesivir interacted with both the finger and palm regions, while one ligand interacted with the finger and thumb regions. Others interacted either with the finger (n = 5) or palm (n = 3) regions. These various interactions have the potential to alter the structural integrity and conformation of the RdRp protein and, in the process, interfere with its role in replication. ConclusionThe findings indicate that the selected medicinal plants possess bioactive compounds that hold great promise for the development of newer and safer nucleoside inhibitors against HCV. Given the high diversity of the virus, there may be a need to expand the scope of genotype-specific treatment regimens using bioactive compounds from medicinal plants. List of Abbreviations and UnitsAA, Amino Acid; HCV, Hepatitis C Virus; HBV, Hepatitis B Virus; GC–MS, Gas chromatograph-mass spectrophotometer; MD, Molecular docking; PDB, Protein Data Bank; RdRp, RNA directed RNA polymerase; RNA, Ribonucleic Acid; HIV, Human Immunodeficiency virus; NIST, National Institute of Standards and Technology; WHO, World Health Organization