Research Article | Volume 11, Issue 1, January, 2023
In silico studies of viral protein inhibitors of Marburg virus using phytochemicals from Andrographis paniculata
The Marburg virus is a causative agent of Marburg hemorrhagic fever, which was discovered in Marburg, Germany, in 1967. It is a highly contagious and fatal disease transmitted by body fluids. The reservoir host is African fruit bats. Currently, there is no vaccine available to control this disease. Medicinal plants possess many phytochemicals of great therapeutic value. Many have antiviral properties and have been identified as promising drug molecules against various viral diseases proven with an in silico approach. The current research uses the in silico approach to identify the phyto-derived drugs from Andrographis paniculata to treat the Marburg virus. Twenty-four bioactive molecules from the A. paniculata plant were investigated against the targets VP35 and VP40 of Marburg viral proteins using the AutoDock Vina 1.1.2 tool. Out of 24 compounds, Andrographidine C, Andrographidine A, Andrographolactone, and 7-O-methylwogonin showed best docking scores for the target VP40 dimer while Bisandrographolide A, Luteolin Andrographolide, and Andrographiside showed best docking scores with VP35 protein. To determine the druglikeness, pharmacokinetic and pharmacodynamic properties and toxicity for each target’s highest docking score compound was assessed using the Swiss absorption, distribution, metabolism, and excretion (ADME) and pkCSM tool. Andrographidine C and Andrographolide performed well in all the parameters of ADME and toxicity. These compounds are recommended as effective inhibitors of VP35 and VP40 of Marburg virus and potential antiviral drugs to treat the hemorrhagic disease. Furthermore, in vitro and in vivo studies can be used to examine the effectiveness and mode of action against the proteins of the Marburg virus.
Hariprasath R, Akashpriya C, Veerappa Lakshmaiah V, Praveen N. In silico studies of viral protein inhibitors of Marburg virus using phytochemicals from Andrographis paniculata. J Appl Biol Biotech, 2023;11(01):151-160. https://doi.org/10.7324/JABB.2023.110121
1. Mehedi M, Groseth A, Feldmann H, Ebihara H. Clinical aspects of Marburg hemorrhagic fever. Fut Virol 2011;6(9):1091-106. https://doi.org/10.2217/fvl.11.79 | |
2. Shifflett K, Marzi A. Marburg virus pathogenesis-differences and similarities in humans and animal models. J Viriol 2019;16(1):1-12. https://doi.org/10.1186/s12985-019-1272-z | |
3. Sboui S, Tabbabi A. Marburg virus disease: a review of literature. J Genes Proteins 2017;1:1. | |
4. Byron EE Martina ADO. "Filoviruses": a real pandemic threat? EMBO Mol Med 2009;1(1):10. https://doi.org/10.1002/emmm.200900005 | |
5. Olejnik J, Mühlberger E, Hume AJ. Recent advances in Marburg virus research. F1000 Res 2019;8. https://doi.org/10.12688/f1000research.17573.1 | |
6. Bamberg S, Kolesnikova L, Möller P, Klenk H-D, Becker S. VP24 of Marburg virus influences formation of infectious particles. J Virol 2005;79(21):13421-33. https://doi.org/10.1128/JVI.79.21.13421-13433.2005 | |
7. Tigabu B, Ramanathan P, Ivanov A, Lin X, Ilinykh PA, Parry CS, et al. Phosphorylated VP30 of Marburg virus is a repressor of transcription. J Virol 2018;92. https://doi.org/10.1128/JVI.00426-18 | |
8. Wenigenrath J, Kolesnikova L, Hoenen T, Mittler E, Becker S. Establishment and application of an infectious virus-like particle system for Marburg virus. J Gen Virol 2010;91: 1325-34. https://doi.org/10.1099/vir.0.018226-0 | |
9. Ramanan P, Edwards MR, Shabman RS, Leung DW, Endlich-Frazier AC, Borek DM, et al. Structural basis for Marburg virus VP35- mediated immune evasion mechanisms. Proc Natl Acad Sci USA 2012;109(50):20661-6. https://doi.org/10.1073/pnas.1213559109 | |
10. Leroy E, Baize S Gonzalez JP. Ebola and Marburg hemorrhagic fever viruses: update on filoviruses. Medecine Tropicale: Revue Du Corps de Sante Colonial 2011;71(2). | |
11. Diaz LX, Ortega JO, Lopez KAL, Garcia IV, Gutierrez JLC. 2526. Side effects of antiretroviral therapy in children with HIV in a referral center in Mexico. Open Forum Infect Dis 2019;6:S878. https://doi.org/10.1093/ofid/ofz360.2204 | |
12. Karunamoorthi K, Jegajeevanram K, Vijayalakshmi J, Mengistie E. Traditional medicinal plants: a source of phytotherapeutic modality in resource-constrained health care settings. J Evid Based Complem Altern Med 2013;18(1):67-74. https://doi.org/10.1177/2156587212460241 | |
13. Ekor M. The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Front Pharmacol 2014;4. https://doi.org/10.3389/fphar.2013.00177 | |
14. Hossain MS, Urbi Z, Sule A, Rahman KMH. Andrographis paniculata (Burm. f.) Wall. Ex Nees: a review of ethnobotany, phytochemistry, and pharmacology. Sci World J 2014;16. https://doi.org/10.1155/2014/274905 | |
15. Okhuarobo A, Falodun JE, Erharuyi O, Imieje V, Falodun A, Langer P. Harnessing the medicinal properties of Andrographi spaniculata for diseases and beyond: a review of its phytochemistry and pharmacology. Asian Pac J Trop Dis 2014;4(3):213. https://doi.org/10.1016/S2222-1808(14)60509-0 | |
16. Hossain MU, Khan MA, Rakib-Uz-Zaman SM, Ali MT, Islam MS, Keya CA, et al. Treating diabetes mellitus: pharmacophore based designing of potential drugs from Gymnema sylvestre against insulin receptor protein. Biomed Res Int 2016;2016. https://doi.org/10.1155/2016/3187647 | |
17. Adeniji S, Uba S, Uzairu A. In silico study for evaluating the binding mode and interaction of 1, 2, 4-triazole and its derivatives as potent inhibitors against Lipoate protein B (LipB). J King Saud Univ Sci 2020;32(1):475-85. https://doi.org/10.1016/j.jksus.2018.07.014 | |
18. Chandrasekaran CV, Gupta A, Agarwal A. Effect of an extract of Andrographis paniculata leaves on inflammatory and allergic mediators in vitro. J Ethnopharmacol 2010;129(2):203-7. https://doi.org/10.1016/j.jep.2010.03.007 | |
19. Singha PK, Roy S, Dey S. Antimicrobial activity of Andrographis paniculata. Fitoterapia 2003;74(7-8):692-4. https://doi.org/10.1016/S0367-326X(03)00159-X | |
20. Diniz WJS, Canduri F. Bioinformatics: an overview and its applications. Genet Mol Res 2017;16(1). https://doi.org/10.4238/gmr16019645 | |
21. Nag A, Chowdhury RR. Piperine, an alkaloid of black pepper seeds can effectively inhibit the antiviral enzymes of Dengue and Ebola viruses, an in silico molecular docking study. Virusdisease 2020;31(3):308-15. https://doi.org/10.1007/s13337-020-00619-6 | |
22. Eberhardt J, Santos-Martins D, Tillack AF, Forli S. AutoDock Vina 1.2.0. New docking methods, expanded force field, and python bindings. J Chem Inf Model 2021;61(8):3891-8. https://doi.org/10.1021/acs.jcim.1c00203 | |
23. Thakur L, Vadhera P, Yadav N. Combating sars-cov-19 by phytochemicals: an in silico study. Innov J Life Sci 2020;8(4):1-4. | |
24. Joshi T, Joshi T, Sharma P, Mathpal S, Pundir H, Bhatt V, Chandra S. 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). | |
25. Qawoogha SS, Shahiwala A. Identification of potential anticancer phytochemicals against colorectal cancer by structure-based docking studies. J Recept Signal Transduct Res 2020;40(1):67-76. https://doi.org/10.1080/10799893.2020.1715431 | |
26. Rutwick Surya U, Praveen N. A molecular docking study of SARS-CoV-2 main protease against phytochemicals of Boerhaavia diffusa Linn. for novel COVID-19 drug discovery. Virusdisease 2021;32(1):1-9. https://doi.org/10.1007/s13337-021-00683-6 | |
27. Umadevi P, Manivannan S, Fayad AM, Shelvy S. Analysis of phytochemicals as potential inhibitors of proteases involved in SARSCoV-2 infection. J Biomol Struct Dyn 2020:1-9. https://doi.org/10.1080/07391102.2020.1866669 | |
28. Oda SI, Noda T, Wijesinghe KJ, Halfmann P, Bornholdt ZA, Abelson DM, et al. Crystal structure of Marburg virus VP40 reveals a broad, basic patch for matrix assembly and a requirement of the N-terminal domain for immunosuppression. J Virol 2016;90(4):1839-48. https://doi.org/10.1128/JVI.01597-15 | |
29. Ullah A, Prottoy NI, Araf Y, Hossain S, Sarkar B, Saha A. Molecular docking and pharmacological property analysis of phytochemicals from Clitoria ternatea as potent inhibitors of cell cycle checkpoint proteins in the cyclin/CDK pathway in cancer cells. Comput Mol Biosci 2019;09(03):81-94. https://doi.org/10.4236/cmb.2019.93007 | |
30. Trott O, Olson AJ. AutoDockVina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2010;31(2):455-61. https://doi.org/10.1002/jcc.21334 | |
31. Nisha CM, Kumar A, Nair P, Gupta N, Silakari C, Tripathi T, et al. Molecular docking and in silico ADMET study reveals Acylguanidine 7a as a potential inhibitor of β-Secretase. Adv Bioinformatics 2016;2016:9258578. https://doi.org/10.1155/2016/9258578 | |
32. Enmozhi, SK, Raja K, Sebastine I, Joseph J. Andrographolide as a potential inhibitor of SARS-CoV-2 main protease: an in silico approach. J Biomol Struct Dyn 2021;39(9):3092-8. https://doi.org/10.1080/07391102.2020.1760136 | |
33. Hiremath S, Kumar HDV, Nandan M, Mantesh M, Shankarappa KS, Venkataravanappa V, et al. In silico docking analysis revealed the potential of phytochemicals present in Phyllanthus amarus and Andrographis paniculata, used in Ayurveda medicine in inhibiting SARS-CoV-2. 3 Biotech 2021;11(2). https://doi.org/10.1007/s13205-020-02578-7 | |
34. Bhosale S, Kumar A. Screening of phytoconstituents of Andrographis paniculata against various targets of Japanese encephalitis virus: an in-silico and in-vitro target-based approach. Curr Res Pharmacol Drug Discov 2021;2(100043):100043. https://doi.org/10.1016/j.crphar.2021.100043 | |
35. Van de Waterbeemd H, Gifford E. ADMET in silico modelling: towards prediction paradise? Nat Rev Drug Discov 2003;2(3):192-204. https://doi.org/10.1038/nrd1032 | |
36. Wang W, Donini O, Reyes CM, Kollman PA. Biomolecular simulations: recent developments in force fields, simulations of enzyme catalysis, protein-ligand, protein-protein, and protein-nucleic acid non-covalent interactions. Annu Rev Biophys Biomol Struct 2001;30:211-43. https://doi.org/10.1146/annurev.biophys.30.1.211 | |
37. Forli S, Huey R, Pique ME, Sanner MF, Goodsell DS, Olson AJ. Computational protein-ligand docking and virtual drug screening with the AutoDock suite. Nat Protocol 2016;11(5):905-19. https://doi.org/10.1038/nprot.2016.051 | |
38. Morris GM, Lim-Wilby M. Molecular docking. Methods Mol Biol 2008;443:365-82. https://doi.org/10.1007/978-1-59745-177-2_19 | |
39. Tanchuk VY, Tanin VO, VovkAI,Poda G. A New, improved hybrid scoring function for molecular docking and scoring based on AutoDock and AutoDockVina. Chem Biol Drug Design 2016;87(4):618-25. https://doi.org/10.1111/cbdd.12697 | |
40. Azam SS, Abbasi SW. Molecular docking studies for the identification of novel melatoninergic inhibitors for acetylserotoninO-methyltransferase using different docking routines. Theor Biol Med Model2013;10(1):1-16. https://doi.org/10.1186/1742-4682-10-63 | |
41. Sharmila R, Jaikumar B. Molecular docking study of bioactive compound of andrographolide against ebola virus. Int J Pharma Sci Res 2016;7(5):250-3. | |
42. Cheng F, Li W, Liu G, Tang Y. In silico ADMET prediction: recent advances, current challenges and future trends. Curr Top Med Chem 2013;13(11):1273-89. https://doi.org/10.2174/15680266113139990033 | |
43. Subash R. In silico pharmacokinetic and toxicological properties prediction of bioactive compounds from Andrographis paniculata. Natl J Physiol Pharm Pharmacol 2020;(0):1. https://doi.org/10.5455/njppp.2020.10.02040202022042020 | |
44. Vincent S, Arokiyaraj S, Saravanan M, Dhanraj M. Molecular docking studies on the anti-viral effects of compounds from Kabasura Kudineer on SARS-CoV-2 3CL. Front Mol Biosci 2021;7:613401. https://doi.org/10.3389/fmolb.2020.613401 | |
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