IN SILICO ANALYSIS AND DOCKING STUDY OF THE ACTIVE PHYTO COMPOUNDS OF MORINGA OLEIFERA AGAINST MARBURG VIRUS VP35 PROTEIN
DOI:
https://doi.org/10.22159/ijs.2022.v10i1.46218Keywords:
Marburg virus, VP35 protein, Docking, Nonstructural proteins, Viral replication, Moringa oleiferaAbstract
Objective: Marburg is a transmissible disease of the Filoviridae family. It infected a million people worldwide. Hence, an attempt was made to identify natural compounds from Moringa oleifera, having multiple medicinal values in Indian Ayurveda, to prevent the disease, using molecular docking, drug likeness prediction, absorption, distribution, metabolism, and excretion (ADME) analysis, and toxicity prediction.
Methods: Marburg main protein was retrieved from the protein data bank database. The ligands with poor binding and molecules that can affect docking were removed and docking is done with the PyRx tool. ADME and drug-likeness analysis were done using Swiss-ADME and absorption, distribution, metabolism, excretion, and toxicity (ADMET) lab web server.
Results: Ramachandran plot analysis shows the statistical distribution of the combinations of the backbone dihedral angles ϕ and ψ of the protein. Molecular docking studies show three compounds from M. oleifera have potential binding affinity to resist the main protein VP35 by preventing proteolytic cleavage, translation, and replication of the virus. ADMET profile and drug likeness and toxicity prediction showed that all three compounds Melanin, Diclazuril, and Tifentai were safe and possess drug-like properties.
Conclusion: The present study suggests that Melanin, Diclazuril, and Tifentai have significant binding affinity and they could inhibit the main protein VP35 and also helps to manage the therapeutic strategies against Marburg Virus.
References
Adjemian J, Farnon EC, Tschioko F, Wamala JF, Byaruhanga E, Bwire GS, et al. Outbreak of Marburg hemorrhagic fever among miners in Kamwenge and Ibanda districts, Uganda, 2007. J Infect Dis 2011;204:S796-9.
WHO. Marburg Virus Disease. Ghana: WHO; 2022. Available from: https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON402 [Last accessed on 2022 Sep 09].
Iastate. Ebolavirus and Marburgvirus Infections. Ames: Iastate; 2021 Available from: https://www.cfsph.iastate.edu/Factsheets/pdfs/viral_hemorrhagic_fever_filovirus.pdf [Last accessed on 2022 Sep 09].
Kortepeter MG, Dierberg K, Shenoy ES, Cieslak TJ, Medical Countermeasures Working Group of the National Ebola Training and Education Center’s, Special Pathogens Research Network. Marburg virus disease: A summary for clinicians. Int J Infect Dis 2020;99:233-42.
Kuhn JH, Becker S, Ebihara H, Geisbert TW, Johnson KM, Kawaoka Y, et al. Proposal for a revised taxonomy of the family Filoviridae: Classification, names of taxa and viruses, and virus abbreviations. Arch Virol 2010;155:2083-103.
Bosio CM, Aman MJ, Grogan C, Hogan R, Ruthel G, Negley D, et al. Ebola and Marburg viruses replicate in monocyte-derived dendritic cells without inducing the production of cytokines and full maturation. J Infect Dis 2003;188:1630-8.
Martini GA, Knauff HG, Schmidt HA, Mayer G, Baltzer G. On the hitherto unknown, in monkeys originating infectious disease: Marburg virus disease. Dtsch Med Wochenschr 1968;93:559-71.
Peterson AT, Lash RR, Carroll DS, Johnson KM. Geographic potential for outbreaks of Marburg hemorrhagic fever. Am J Trop Med Hyg 2006;75:9-15.
Quazi S, Gavas S, Malik JA, Suman KS, Haider Z. In-silico pharmacophore and Molecular Docking based drug discovery against Marburg Virus’s Viral Protein 35; A potent of MAVD. BioRxiv 2021.
Hartman AL, Towner JS, Nichol ST. A C-terminal basic amino acid motif of Zaire ebolavirus VP35 is essential for Type I interferon antagonism and displays high identity with the RNA-binding domain of another interferon antagonist, the NS1 protein of influenza A virus. Virology 2004;328:177-84.
Timen A. Response to imported case of Marburg hemorrhagic fever, the Netherlands. Emerg Infect Dis 2009;15:1171-5.
Zhu W, Zhang Z, He S, Wong G, Banadyga L, Qiu X. Successful treatment of Marburg virus with orally administrated T-705 (Favipiravir) in a mouse model. Antiviral Res 2018;151:39-49.
Singh RH, Narsimhamurthy K, Singh G. Neuronutrient impact of Ayurvedic Rasayana therapy in brain aging. Biogerontology 2008;9:369-74.
Researchgate. Moringa Oleifera – Nature’s Gold. Berlin: ResearchGate; 2017. Available from: https://www.researchgate.net/publication/317930958_Moringa_Oleifera_-_Nature’s_Gold [Last accessed on 2022 Sep 09].
Fajri M. The potential of Moringa oleifera as immune booster against COVID 19. IOP Conf Ser Earth Environ Sci 2021;807:022008.
Iqbal Khan R, Abbas M, Goraya K, Zafar-Ul-Hye M, Danish S. Plant derived antiviral products for potential treatment of COVID-19: A review. Phyton Int J Exp Bot 2020;89:438-52.
Paikra BK, Dhongade HK, Gidwani B. Phytochemistry and pharmacology of Moringa oleifera Lam. J Pharmacopuncture 2017;20:194-200.
Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, et al. The protein data bank. Nucleic Acids Res 2000;28:235-42.
European Bioinformatics Institute. PDBsum Home Page. Cambridge: European Bioinformatics Institute. Available from: https://www.ebi.ac.uk/pdbsum [Last accessed on 2022 Sep 09].
Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, et al. PubChem in 2021: New data content and improved web interfaces. Nucleic Acids Res 2021;49:D1388-95.
McConkey BJ, Sobolev V, Edelman M. The performance of current methods in ligand-protein docking. Curr Sci 2002;83:845-56.
Trott O, Olson AJ. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2010;31:455-61.
O’Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR. Open Babel: An open chemical toolbox. J Cheminform 2011;3:33.
Biovia DS. Discovery Studio Modeling Environment. Vélizy-Villacoublay: Dassault Syst, Release, San Diego, Scirp.org; 2015. Available from: https://www.scirp.org/(S(351jmbntv-nsjt1aadkposzje))/reference/referencespapers.aspx?referenceid=2450411 [Last accessed on 2022 Sep 09].
Wikipedia Contributors. ADME. Wikipedia, The Free Encyclopedia; 2022. Available from: https://en.wikipedia.org/w/index.php?title=ADME&oldid=1087865915 [Last accessed on 2022 Sep 09].
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;7:42717.
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:W5-14.
Daina A, Zoete V. A BOILED-Egg to predict gastrointestinal absorption and brain penetration of small molecules. ChemMedChem 2016;11:1117-21.
Published
How to Cite
Issue
Section
Copyright (c) 2022 SHIVAM CHAVAN, SHUBHAM WANARASE, SAMEER SHARMA
![Creative Commons License](http://i.creativecommons.org/l/by/4.0/88x31.png)
This work is licensed under a Creative Commons Attribution 4.0 International License.