In- silico evaluation of bioactive compounds from selected medicinal plants from Southern Nigeria against hepatitis C virus genotype 1 RNA-directed RNA polymerase
Background: At 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 sea...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Scientific African |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468227623003745 |
| _version_ | 1797429644611289088 |
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| author | Clement I. Mboto Uwem O. Edet Elizabeth N. Mbim Wilfred O. Ndifon Eno E. Ebenso Henry O. Egharevba Uwem E. George Francisca O. Nwaokorie Samuel.I. Udo |
| author_facet | Clement I. Mboto Uwem O. Edet Elizabeth N. Mbim Wilfred O. Ndifon Eno E. Ebenso Henry O. Egharevba Uwem E. George Francisca O. Nwaokorie Samuel.I. Udo |
| author_sort | Clement I. Mboto |
| collection | DOAJ |
| description | Background: At 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). Methods: Traditional 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. Results: GC–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. Conclusion: The 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 Units: AA, 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 |
| first_indexed | 2024-03-09T09:16:06Z |
| format | Article |
| id | doaj.art-b7cd35a30f164457833b1fe59b54af38 |
| institution | Directory Open Access Journal |
| issn | 2468-2276 |
| language | English |
| last_indexed | 2024-03-09T09:16:06Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Scientific African |
| spelling | doaj.art-b7cd35a30f164457833b1fe59b54af382023-12-02T07:06:19ZengElsevierScientific African2468-22762023-11-0122e01919In- silico evaluation of bioactive compounds from selected medicinal plants from Southern Nigeria against hepatitis C virus genotype 1 RNA-directed RNA polymeraseClement I. Mboto0Uwem O. Edet1Elizabeth N. Mbim2Wilfred O. Ndifon3Eno E. Ebenso4Henry O. Egharevba5Uwem E. George6Francisca O. Nwaokorie7Samuel.I. Udo8Department of Microbiology, Faculty of Biological Science, University of Calabar, Calabar, Cross River State, Nigeria; Viro-Bio Research Laboratory, Department of Microbiology, Faculty of Biological Science, University of Calabar, Calabar, Cross River State, NigeriaViro-Bio Research Laboratory, Department of Microbiology, Faculty of Biological Science, University of Calabar, Calabar, Cross River State, Nigeria; Department of Biological (Microbiology), Faculty of Natural and Applied Sciences, Arthur Jarvis University, Akpabuyo, Cross River State, Nigeria; Corresponding author at: Viro-Bio Research Laboratory, Department of Microbiology, Faculty of Biological Science, University of Calabar, Calabar, Cross River State, Nigeria.Viro-Bio Research Laboratory, Department of Microbiology, Faculty of Biological Science, University of Calabar, Calabar, Cross River State, Nigeria; Department of Public Health, Faculty of Basic Medical Sciences, Arthur Jarvis University, Akpabuyo, Cross River State, NigeriaDepartment of Community Medicine, University of Calabar, Calabar, NigeriaCentre for Material Science, College of Science, Engineering and Technology, University of South Africa, Florida Campus, Johannesburg 1709 South AfricaNational Institute for Pharmaceutical Research and Development (NIPRD), Idu Industrial Layout Idu, Garki, Abuja, NigeriaAfrican Centre of Excellence for Genomics of Infectious Diseases, College of Natural Science, Redeemer's University, Ede, Osun, off Ibadan-Oshogbo Road, Osun State, NigeriaDepartment of Medical Laboratory Sciences, College of Medicine, University of Lagos, Lagos State, NigeriaDepartment of Biological Sciences, Cross River University of Technology, Calabar, Cross River state, NigeriaBackground: At 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). Methods: Traditional 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. Results: GC–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. Conclusion: The 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 Units: AA, 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 Organizationhttp://www.sciencedirect.com/science/article/pii/S2468227623003745DockingBioactive compoundsMedicinal plantsHCVGenotype 1Drug target |
| spellingShingle | Clement I. Mboto Uwem O. Edet Elizabeth N. Mbim Wilfred O. Ndifon Eno E. Ebenso Henry O. Egharevba Uwem E. George Francisca O. Nwaokorie Samuel.I. Udo In- silico evaluation of bioactive compounds from selected medicinal plants from Southern Nigeria against hepatitis C virus genotype 1 RNA-directed RNA polymerase Scientific African Docking Bioactive compounds Medicinal plants HCV Genotype 1 Drug target |
| title | In- silico evaluation of bioactive compounds from selected medicinal plants from Southern Nigeria against hepatitis C virus genotype 1 RNA-directed RNA polymerase |
| title_full | In- silico evaluation of bioactive compounds from selected medicinal plants from Southern Nigeria against hepatitis C virus genotype 1 RNA-directed RNA polymerase |
| title_fullStr | In- silico evaluation of bioactive compounds from selected medicinal plants from Southern Nigeria against hepatitis C virus genotype 1 RNA-directed RNA polymerase |
| title_full_unstemmed | In- silico evaluation of bioactive compounds from selected medicinal plants from Southern Nigeria against hepatitis C virus genotype 1 RNA-directed RNA polymerase |
| title_short | In- silico evaluation of bioactive compounds from selected medicinal plants from Southern Nigeria against hepatitis C virus genotype 1 RNA-directed RNA polymerase |
| title_sort | in silico evaluation of bioactive compounds from selected medicinal plants from southern nigeria against hepatitis c virus genotype 1 rna directed rna polymerase |
| topic | Docking Bioactive compounds Medicinal plants HCV Genotype 1 Drug target |
| url | http://www.sciencedirect.com/science/article/pii/S2468227623003745 |
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