COMBATING SARS-COV-19 BY PHYTOCHEMICALS: AN IN SILICO STUDY
Keywords:
Coronavirus, COVID-19 main protease, Phytochemicals, Molecular Docking, Receptor-ligand Interaction AutoDock Vina, Chimera 1131, Discovery studioAbstract
Objective: The objective of the study was to identify the potential lead phytochemical compounds that can be targeted against the severe acute respiratory coronavirus, 2019 (SARS-CoV-19) main protease (6LU7).
Method: A total of 191 phytochemicals from the Phytochemical and Drug Target Database (PDTDB) were retrieved and screened against SARS-CoV-19 protease by employing computational molecular docking studies.
Results: Our molecular docking results reveal that compounds ergosterol peroxide, punicalin, oleanolic acid, naringin, and diosmin are showing a very good affinity for coronavirus disease, 2019 (COVID-19) main protease and can be explored further as the lead candidate.
Conclusion: Computational studies of phytochemicals library against 6LU, a SARS-CoV-19 main protease led to the determination of compounds with the best theoretical affinity. Further, more target information of these compounds is needed for drug intervention, rational drug design, in vitro and in vivo evaluations, and final preparation in terms of clinical trial so that they can be used to combat the novel virus SARS-CoV-19.
References
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506.
Brook CE, Boots M, Chandran K, Dobson AP, Drosten C, Graham AL, et al. Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence. Elife 2020;9:e48401.
Wu C, Liu Y, Yang Y, Zhang P, Zhong W, Wang Y, et al. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm Sin B 2020;10:766-88.
Su S, Wong G, Shi W, Liu J, Lai AC, Zhou J, et al. Epidemiology, genetic recombination, and pathogenesis of coronaviruses. Trends Microbiol 2016;24:490-502.
Bosch BJ, Van Der Zee R, De Haan CA, Rottier PJ. The coronavirus spike protein is a class I virus fusion protein: Structural and functional characterization of the fusion core complex. J Virol 2003;77:8801-11.
Ge XY, Li JL, Yang XL, Chmura AA, Zhu G, Epstein JH, et al. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature 2013;503:535-8.
Yang H, Yang M, Ding Y, Liu Y, Lou Z, Zhou Z, et al. The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor. Proc Natl Acad Sci U S A 2003;100:13190-5.
Zhang D, Wu K, Zhang X, Deng S, Peng B. In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus. J Integr Med 2020;18:152-8.
Yang Y, Islam MS, Wang J, Li Y, Chen X. Traditional Chinese medicine in the treatment of patients infected with 2019-new coronavirus (SARS-CoV-2): A review and perspective. Int J Biol Sci 2020;16:1708-17.
Kumar TA, Rajagopal B. PDTDB-an integrative structural database and prediction server for plant metabolites and therapeutic drug targets. Int J Curr Res 2017;9:46537-41.
Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, et al. UCSF Chimera--a visualization system for exploratory research and analysis. J Comput Chem 2004;25:1605-12.
O’Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR. Open babel: An open chemical toolbox. J Cheminform 2011;3:33.
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.
Dallakyan S, Olson AJ. Small-molecule library screening by docking with PyRx. Methods Mol Biol 2015;1263:243-50.
Dassault Systèmes. BIOVIA, Discovery Studio. Modeling Environment. San Diego: Dassault Systèmes; 2020.
Hsu CH, Hwang KC, Chao CL, Chang SG, Ho MS, Lin JG, et al. An evaluation of the additive effect of natural herbal medicine on SARS or SARS-like infectious diseases in 2003: A randomized, double-blind, and controlled pilot study. Evid Based Complement Altern Med 2008;5:355-62.
Gajalakshmi S, Vijayalakshmi S, Rajeswari D. Phytochemical and pharmacological properties of Annona muricata: A review. Int J Pharm Pharm Sci 2012;4:3-6.
Venkatesan A, Kothandan S, Radhakrishnan A, Kuppuswamy G, Palanisamy D, Somanathan B, et al. Treatments and prophylactics for a global emergency alert: COVID 19 using allopathic and Indian phytomedicine. Int J Res Pharm Sci 2020;11:68-76.
Merdivan S, Lindequist U. Ergosterol peroxide: A mushroom-derived compound with promising biological activities-a review. Int J Med Mushrooms 2017;19:93-105.
Lindequist U, Niedermeyer TH, Jülich WD. The pharmacological potential of mushrooms. Evid Based Complement Altern Med 2005;2:285-99.
Zhang Y, Wang D, Lee RP, Henning SM, Heber D. Absence of pomegranate ellagitannins in the majority of commercial pomegranate extracts: Implications for standardization and quality control. J Agric Food Chem 2009;57:7395-400.
Viladomiu M, Hontecillas R, Lu P, Bassaganya-Riera J. Preventive and prophylactic mechanisms of action of pomegranate bioactive constituents. Evid Based Complement Altern Med 2013;2013:789764.
Marquez-Martin A, De La Puerta R, Fernandez-Arche A, Ruiz- Gutierrez V, Yaqoob P. Modulation of cytokine secretion by pentacyclic triterpenes from olive pomace oil in human mononuclear cells. Cytokine 2006;36:211-7.
Alam MA, Subhan N, Rahman MM, Uddin SJ, Reza HM, Sarker SD. Effect of citrus flavonoids, naringin and naringenin, on metabolic syndrome and their mechanisms of action. Adv Nutr 2014;5:404-17.
Feldo M, Wo?niak M, Wójciak-Kosior M, Sowa I, Kot-Wa?ik A, Aszyk J, et al. Influence of diosmin treatment on the level of oxidative stress markers in patients with chronic venous insufficiency. Oxid Med Cell Longev 2018;2018:2561705.