Computational Screening of Medicinal Plant Phytochemicals to Discover Potent Inhibitors against Hepatitis B Virus
Journal of Advances in Biology & Biotechnology,
Hepatitis B virus (HBV) infections are infamous to cause liver damage, hepatocellular carcinoma, and cirrhosis, all of which can be fatal in nature. Nucleotide analogues, which target viral reverse transcriptase, and interferon therapy, which is known to have side effects in recipients, are currently being used to treat such infections. Increasingly, the growing viral resistance towards the first line of drugs has been a concern for the healthcare system worldwide, and therefore the need for new therapeutic interventions has been noted and novel viral targets are being explored. The HBV core protein (HBc), which regulates several viral replication checkpoints in the host cell, is one such possible target for therapeutic development. In this study, we use in silico approach to investigate the potential of various phytochemicals and natural compounds to be developed as antiviral medicines that target HBc protein. For which, the compounds were collected from databases and potential candidates were screened and shortlisted based on their pharmacokinetics and drug-likeness using Lipinski’s rule of five. Further, the chosen phytochemicals were subjected to docking analysis, and binding affinities were evaluated to set a cut-off value for selecting the best interactions, which showed better binding energy values compared to standard anti-HBV drugs. Further, the two- and three-dimensional interactions of the ligand and target protein complexes were studied to gain insights into the ligand-target bonding patterns, and bioavailability and toxicity profiles were analyzed to understand the safety and efficacy of the selected compounds to be developed as anti-HBV interventions. Upon complete inspection, Ingenol was identified as the best candidate among the chosen phytochemicals, followed by I-asarinin and Withaferin. We hope that the findings from this study will be useful in the development of anti-HBV drug candidates or formulations.
- Molecular docking
- toxicity testing
- binding energy
- core protein
- hepatocellular carcinoma
How to Cite
Carlos Ferraz Da Fonseca J. Histórico das hepatites virais History of viral hepatitis. Vol. 43, INTRODUçãO Revista da Sociedade Brasileira de Medicina Tropical; 2010.
Castaneda D, Gonzalez AJ, Alomari M, Tandon K, Zervos XB. From hepatitis A to E: A critical review of viral hepatitis. World J Gastroenterol. 2021;27(16):1691–715.
Wiktor SZ. Viral Hepatitis. Dis Control Priorities, Third Ed (Volume 6) Major Infect Dis. 2017 Nov 3;401–9.
Zarrin A, Akhondi H. Viral Hepatitis. StatPearls; 2021.
Jefferies M, Rauff B, Rashid H, Lam T, Rafiq S. Update on global epidemiology of viral hepatitis and preventive strategies. World J Clin cases. 2018;6(13):589–99.
Anzola M. Hepatocellular carcinoma: role of hepatitis B and hepatitis C viruses proteins in hepatocarcinogenesis. J Viral Hepat. 2004;11(5):383–93.
(PDF) The extrahepatic manifestations of Hepatitis B Virus.
Tsai K-N, Kuo C-F, James Ou J-H. Mechanisms of Hepatitis B Virus Persistence.
Samal J, Kandpal M, Vivekanandan P. Molecular Mechanisms Underlying Occult Hepatitis B Virus Infection. Clin Microbiol Rev. 2012;25(1):142.
Aspinall EJ, Hawkins G, Fraser A, Hutchinson SJ, Goldberg D. Hepatitis B prevention, diagnosis, treatment and care: A review. Vol. 61, Occupational Medicine. 2011;531–40.
Mak LY, Wong DKH, Seto WK, Lai CL, Yuen MF. Hepatitis B core protein as a therapeutic target. Expert Opin Ther Targets. 2017;21(12):1153–9.
Petitv M-A, Pillot J. HBc and HBe Antigenicity and DNA-Binding Activity of Major Core Protein P22 in Hepatitis B Virus Core Particles Isolated from the Cytoplasm of Human Liver Cells Purification procedure of core particles from liver. An HBV-infected human liver obtained from a patient on dialysis and screened for the presence of HBcAg in nuclei by immunofluo-rescence was the starting material for the purification. J Virol. 1985;53(2):543–51.
Chen MT, Billaud JN, Sällberg M, Guidotti LG, Chisari F V., Jones J, et al. A function of the hepatitis B virus precore protein is to regulate the immune response to the core antigen. Proc Natl Acad Sci U S A. 2004;101(41):14913–8.
Firdayani, Arsianti A, Churiyah, Yanuar A. Molecular Docking and Dynamic Simulation Studies of Benzoylated Emodin into HBV Core Protein. J Young Pharm. 2018;10(2s):s20–4.
Ahire ED, Sonawane VN, Surana KR, Talele GS. Drug Discovery, Drug-Likeness Screening, and Bioavailability: Development of Drug-Likeness Rule for Natural Products. Appl Pharm Pract Nutraceuticals. 2021;191–208.
Vijayasri S, Hopper W. Towards the Identification of Novel Phytochemical Leads as Macrodomain Inhibitors of Chikungunya Virus Using Molecular Docking Approach. J Appl Pharm Sci. 2017;7(04):74–082.
Das P, Majumder R, Mandal M, Basak P. In-Silico approach for identification of effective and stable inhibitors for COVID-19 main protease (M pro) from flavonoid based phytochemical constituents of Calendula officinalis. J Biomol Struct Dyn. 2021;39(16):6265–80.
Joshi T, Joshi T, Sharma P, Mathpal S, Pundir H, Bhatt V, et al. In silico screening of natural compounds against COVID-19 by targeting Mpro and ACE2 using molecular docking. Eur Rev Med Pharmacol Sci. 2020;24(8):4529–36.
Basu A, Sarkar A, Maulik U. Molecular docking study of potential phytochemicals and their effects on the complex of SARS-CoV2 spike protein and human ACE2. Sci Reports 2020 101. 2020;10(1):1–15.
Yu X, Jin L, Jih J, Shih C, Hong Zhou Z. 3.5Å cryoEM Structure of Hepatitis B Virus Core Assembled from Full-Length Core Protein. PLoS One. 2013;8(9).
RCSB PDB: Homepage.
Dr. Duke’s Phytochemical and Ethnobotanical Databases at NAL.
IMPPAT | IMPPAT: Indian Medicinal Plants, Phytochemistry And Therapeutics.
SwissADME [Internet]. [cited 2021 Nov 1]. Available from: http://www.swissadme.ch/
Rajalakshmanan, Eswaramoorthy, Hailekiros H, Kedir F, Endale M.
In silico Molecular Docking, DFT Analysis and ADMET Studies of Carbazole Alkaloid and Coumarins from Roots of Clausena anisata: A Potent Inhibitor for Quorum Sensing
. Adv Appl Bioinforma Chem. 2021;14:13–24.
UCSF Chimera Home Page [Internet]. [cited 2021 Nov 2]. Available from: https://www.cgl.ucsf.edu/chimera/
PyRx - Virtual Screening Tool — MGLTools [Internet]. [cited 2021 Apr 28]. Available from: http://mgltools.scripps.edu/documentation/links/pyrx-virtual-screening-tool
BIOVIA, Dassault Systèmes, BIOVIA Workbook, Release 2020; BIOVIA Pipeline Pilot, Release 2020, San Diego: Dassault Systèmes, .
Daina A, Michielin O, Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017 Mar 3;7(1):1–13.
ProTox-II - Prediction of TOXicity of chemicals [Internet]. [cited 2021 Nov 2]. Available from: https://tox-new.charite.de/protox_II/
Banerjee P, Eckert AO, Schrey AK, Preissner R. ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res. 2018;46(W1):W257–63.
Xiong G, Wu Z, Yi J, Fu L, Yang Z, Hsieh C, et al. ADMETlab 2.0: an integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Res. 2021;49 (W1):W5–14.
Sangeetha Vani G, Rajarajan S. A Study on in-silico Analysis of Phytochemicals targeting the proteins of Hepatitis B and C Virus. IntJCurrMicrobiolAppSci. 2015; 4(12):683–91.
Qawoogha SS, Shahiwala A. Identification of potential anticancer phytochemicals against colorectal cancer by structure-based docking studies. J Recept Signal Transduct Res. 2020 Jan 2;40(1):67–76.
Mustafa G, Majid M, Ghaffar A, Yameen M, Samad HA, Mahrosh HS. Screening and molecular docking of selected phytochemicals against NS5B polymerase of hepatitis c virus. Pak J Pharm Sci. 2020 Sep 1;33(5(Supplementary)):2317–22.
Mak LY, Wong DKH, Seto WK, Lai CL, Yuen MF. Hepatitis B core protein as a therapeutic target. Vol. 21, Expert Opinion on Therapeutic Targets. Taylor and Francis Ltd; 2017. p. 1153–9.
Tsai KN, Kuo CF, Ou JHJ. Mechanisms of Hepatitis B Virus Persistence. Trends Microbiol. 2018;26(1):33–42.
Pollastri MP. Overview on the Rule of Five. Curr Protoc Pharmacol. 2010;Chapter 9(SUPPL. 49).
Chen X, Li H, Tian L, Li Q, Luo J, Zhang Y. Analysis of the Physicochemical Properties of Acaricides Based on Lipinski’s Rule of Five. J Comput Biol. 2020;27(9):1397–406.
Li HZ, Ren Z, Reddy N V., Hou T, Zhang ZJ. In silico evaluation of antimicrobial, antihyaluronidase and bioavailability parameters of rosmarinic acid in Perilla frutescens leaf extracts. SN Appl Sci. 2020;2(9).
Vijayakumar M, Janani B, Kannappan P, Renganathan S, Al-Ghamdi S, Alsaidan M, et al. In silico identification of potential inhibitors against main protease of SARS-CoV-2 6LU7 from Andrographis panniculata via molecular docking, binding energy calculations and molecular dynamics simulation studies. Saudi J Biol Sci; 2021.
Tripathi P, Ghosh S, Nath Talapatra S. Bioavailability prediction of phytochemicals present in Calotropis procera (Aiton) R. Br. by using Swiss-ADME tool. World Sci News. 2019;131:147–63.
Bahadur Gurung A, Ajmal Ali M, Lee J, Abul Farah M, Mashay Al-Anazi K. Structure-based virtual screening of phytochemicals and repurposing of FDA approved antiviral drugs unravels lead molecules as potential inhibitors of coronavirus 3C-like protease enzyme. J King Saud Univ - Sci. 2020;32(6):2845–53.
Kumar A, Mishra DC, Angadi UB, Yadav R, Rai A, Kumar D. Inhibition Potencies of Phytochemicals Derived from Sesame Against SARS-CoV-2 Main Protease: A Molecular Docking and Simulation Study. Front Chem. 2021;9(October):1–16.
Lakhera S, Devlal K, Ghosh A, Rana M. In silico investigation of phytoconstituents of medicinal herb ‘Piper Longum’ against SARS-CoV-2 by molecular docking and molecular dynamics analysis. Results Chem. 2021;3(September):100199.
Singh P, Chauhan SS, Pandit S, Sinha M, Gupta S, Gupta A, et al. The dual role of phytochemicals on SARS-CoV-2 inhibition by targeting host and viral proteins. J Tradit Complement Med; 2021.
Okano M, Fukamiya N, Tagahara K, Cosentino M, Lee TTY, Morris-Natschke S, et al. Anti-HIV activity of quassinoids. Bioorg Med Chem Lett. 1996;6(6): 701–6.
Sudeep H, Gouthamchandra K, Shyamprasad K. Molecular docking analysis of Withaferin A from Withania somnifera with the Glucose regulated protein 78 (GRP78) receptor and the SARS-CoV-2 mainprotease. Bioinformation. 2020;16(5):411.
Abstract View: 101 times
PDF Download: 25 times