Analysis of molecular interactions between flavones and dengue DENV E – 3 protein by In silico approach

Volume 8, Issue 2, April 2023     |     PP. 27-53      |     PDF (2068 K)    |     Pub. Date: May 15, 2023
DOI: 10.54647/chemistry150313    95 Downloads     160986 Views  

Author(s)

Cecilia Espíndola, Department of Physical Chemistry, University of Seville, C / Profesor García González 1, 41012 Seville, Spain.

Abstract
The DENV dengue virus belongs to the Flaviviridae family, a group of four serotypes that circulate freely in the different endemic regions causing dengue disease. This disease is transmitted by the female Aedes aegypti and Aedes albopictus mosquitoes. Due to the variety of serotypes and genotypes existing in the same zone, it has been difficult to develop a vaccine due to the complexity of the immune response against dengue disease. Flavones such as 7,8-dihydroxyflavone-tropoflavin, 5,6,7-trihydroxyflavone-baicalein, and 3',4',5,6-tetrahydroxyflavone-luteolin show antiviral activity. The different types of H-Bonds, π-π stacking, and π-cation molecular interactions that occur in the tropoflavin, baicalein, and luteolin, and DENV E-3 protein complexes has been analyzed, and different Kbinding has been identified. Similarly, the linkages between the different flavone and DENV E-3 protein domains for the application of the flavones tropoflavin, baicalein, and luteolin as anti-DENV E-3 agents has been analyzed. Results presented in this study could be useful for compound design and antiviral studies.

Keywords
Antiviral pharmacology, Flavones, drug interactions, non-covalent interaction, DENV E-3 protein, Docking molecular, protein interaction.

Cite this paper
Cecilia Espíndola, Analysis of molecular interactions between flavones and dengue DENV E – 3 protein by In silico approach , SCIREA Journal of Chemistry. Volume 8, Issue 2, April 2023 | PP. 27-53. 10.54647/chemistry150313

References

[ 1 ] Tolle M. Mosquito-borne diseases. Curr Probl Pediatr Adolesc. Health Care. 2009; 39:97-140.
[ 2 ] Harapan, H.; Michie, A.; Sasmono, R. T.; Imrie, A. Dengue: A Minireview. Viruses, 2020, 12, 829.
[ 3 ] Messina, J.P.; Brady, O.J.; Scott, T.W.; Zou, C.; Pigott, D.M.; Duda, K.A.; Bhatt, S.; Katzelnick, L.; Howes, R.E.; Battle, K.E.; Simmons, C. P.; Hay S. I. Global spread of dengue virus types: Mapping the 70-year history. Trends Microbiol. 2014, 22, 138–146.
[ 4 ] Weaver, S.C.; Vasilakis, N. Molecular evolution of dengue viruses: Contributions of phylogenetics to understanding the history and epidemiology of the preeminent arboviral disease. Infect. Genet. Evol. 2009, 9, 523–540.
[ 5 ] Hassandarvish, P.; Rothan, H. A.; Rezaei, S.; Yusof, R.; Abubakara, S.; Zandi, K. In silico study on baicalein and baicalin as inhibitors of dengue virus replication. RSC Adv., 2016, 6, 31235.
[ 6 ] Modis, Y.; Ogata, S.; Clements, D.; Harrison, S.C. Variable Surface Epitopes in the Crystal Structure of Dengue Virus Type 3 Envelope Glycoprotein. JOURNAL OF VIROLOGY, Jan. 2005, p. 1223–1231
[ 7 ] Zheng, C-D.; Li, G.; Li, H-Q.; Xu, X-J.; Gao, J-M.; Zhang, A-L. DPPH-Scavenging Activities and Structure-Activity Relationships of Phenolic Compounds. Natural Product Communications. 2010, 5,1759 – 1765.
[ 8 ] Chiang, N-N.; Lin, T-H.; Teng, Y-S.; Sun, Y-C.; Chang, K-H.; Lin, C-Y.; Hsieh-Li, H. M.; Su, M-T.; Chen, C-M.; Lee-Chen, G-J. Flavones 7,8-DHF, Quercetin, and Apigenin Against Tau Toxicity via Activation of TRKB Signaling in 1K280 TauRD-DsRed SH-SY5Y Cells. Front. Aging Neurosci. 2021,13, 758895.
[ 9 ] Gao, Z.; Huang, K.; Yang, X.; Xu, H. Free radical scavenging and antioxidant activities of flavonoids extracted from the radix of Scutellaria baicalensis. Biochimica et Biophysica Acta. 1999. 1472, 643-650.
[ 10 ] Ahmadi, S. M.; Farhoosh, R.; Sharif, A.; Rezaie, M. Structure-Antioxidant Activity Relationships of Luteolin and Catechin. Journal of Food Science. 2020, (85) 2.
[ 11 ] Veitch, N.C.; Grayer, R.J. Chalcones, Dihydrochalcones, and Aurones. In FLAVONOIDS. Chemistry, Biochemistry and Applications; Andersen O. M. and Markham K. R. Eds. CRC Press. Taylor and Francis Group. 2006; Chapter 16. Pp-1003-1071.
[ 12 ] Tsai, F-J.; Lin, C-W.; Lai, C-C.; Lan, Y-C.; Lai, C-H.; Hung, C-H.; Hsueh, K-C.; Lin, T-H.; Chang, H. C.; Wan, L.; Sheu, J. J-C.; Lin, Y-J. Kaempferol inhibits enterovirus 71 replication and internal ribosome entry site (IRES) activity through FUBP and HNRP proteins. Food Chemistry. 2011, 128, 312-322.
[ 13 ] Zandi, K.; Teoh, B-T.; Sam, S-S.; Wong, P-F.; Mustafa, M. R.; AbuBakar, S. Novel antiviral activity of baicalein against dengue virus. BMC Complementary and Alternative Medicine, 2012, 12,214.
[ 14 ] Peng, M.; Watanabe, S.; Ki-C, K. W.; He, Q.; Zhao, Y.; Zhang, Z.; Lai, X.; Luo, D.; Vasudevan, S. G.; Li, G. Luteolin restricts dengue virus replication through inhibition of the proprotein convertase furin. Antiviral Research, 2017, 143, 176-185.
[ 15 ] Wang, L.; Wang, J.; Wang, L.; Ma, S.; Liu, Y. Anti-Enterovirus 71 Agents of Natural Products. Molecules, 2015, 20, 16320-16333.
[ 16 ] Wang, M.; Tao, L.; Xu, H. Chinese herbal medicines as a source of molecules with anti-enterovirus 71 activity. Chin Med. 2016. 11:2.
[ 17 ] Zheng, Y-Z.; Zhou, Y.; Liang, Q.; Chen, D-F.; Guo, R. Theoretical studies on the hydrogen-bonding interactions between luteolin and water: a DFT approach. J Mol Model. 2016, 22: 257.
[ 18 ] Bissantz, C.; Kuhn, B.; Stahl, M. A Medicinal Chemist’s Guide to Molecular Interactions. J. Med. Chem. 2010, 53, 5061–5084.
[ 19 ] Lommerse, J. P. M.; Price, S. L.; Taylor, R. Hydrogen bonding of carbonyl, ether, and ester oxygen atoms with alkanol hydroxyl groups. J. Comput. Chem. 1997, 18, 757–774.
[ 20 ] Taylor, R.; Kennard, O.; Versichel, W. Geometry of the iminocarbonyl (N-H 333 O:C) hydrogen bond. 1. Lone-pair directionality. J. Am. Chem. Soc. 1983, 105, 5761–5766.
[ 21 ] Nobeli, I.; Price, S. L.; Lommerse, J. P. M.; Taylor, R. Hydrogen bonding properties of oxygen and nitrogen acceptors in aromatic heterocycles. J. Comput. Chem. 1997, 18, 2060–2074.
[ 22 ] Nocker, M.; Handschuh, S.; Tautermann, C.; Liedl, K. R. Theoretical Prediction of Hydrogen Bond Strength for use in Molecular Modeling. J. Chem. Inf. Model. 2009, 49, 2067–2076.
[ 23 ] Morris, G. M., Goodsell, D. S., Halliday, R. S., Huey, R., Hart, W. E., Belew, R. K., y Olson, A. J. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. Journal of Computational Chemistry, 19(14): 1998. 1639–1662.
[ 24 ] Wang, R., Lai, L., y Wang, S. Further development and validation of empirical scoring functions for structure-based binding affinity prediction. Journal of computeraided molecular design, 16(1): 2002.11–26.
[ 25 ] Ismail, N. A.; Jusoh, S. A. Molecular Docking and Molecular Dynamics Simulation Studies to Predict Flavonoid Binding on the Surface of DENV2 E Protein. Interdiscip Sci Comput Life Sci. 2017, 9:499–511.
[ 26 ] Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S., & Olson, A. J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. Journal of Computational Chemistry, 2009. 30(16), 2785–2791
[ 27 ] O. Trott, A. J. Olson, AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading, Journal of Computational Chemistry. 2010. 31, 455-461.
[ 28 ] Guirakhoo, F.; Hunt, A. R.; Lewis, J. G.; Roehrig, J. T. Selection and partial characterization of dengue 2 virus mutants that induce fusion at elevated pH. Virology. 1993, 194:219–223
[ 29 ] Hung, S. L.; Lee, P. L.; Chen, H. W.; Chen, L. K.; Kao, C. L.; King, C. C. Analysis of the steps involved in dengue virus entry into host cells. Virology, 1999. 257:156–167.
[ 30 ] Navarro-Sanchez, E.; Altmeyer, R.; Amara, A.; Schwartz, O.; Fieschi, F.; Virelizier, J. L.; Arenzana-Seisdedos, F.; P. Despres, P. Dendritic-cell-specific ICAM3-grabbing non-integrin is essential for the productive infection of human dendritic cells by mosquito-cell-derived dengue viruses. EMBO Rep. 2003. 4, 1–6.
[ 31 ] Modis, Y.; Ogata, S.; Clements, D.; Harrison, S. C. A ligand-binding pocket in the dengue virus envelope glycoprotein. PNAS. 2003, 100, 6986–6991.
[ 32 ] Tassaneetrithep, B.; Burgess, T. H.; Granelli-Piperno, A.; Trumpfheller, C.; Finke, J.; Sun, W.; Eller, M. A.; Pattanapanyasat, K.; Sarasombath, S.; Birx, D. L.; Steinman, R. M.; Schlesinger, S.; Marovich, M. A. DC-SIGN (CD209) mediates dengue virus infection of human dendritic cells. J. Exp. Med. 2003. 197, 823–829.
[ 33 ] Horton H. R.; Moran L. A.; Scrimgeour K. G.; Perry M. D.; Rawn J. D. Principles of Biochemistry. 2006. 4th. Edition. Pearson Education, Inc., Publishing as Prentice Hall. Chapter 3.
[ 34 ] Mondotte, J. A.; Lozach, P-Y.; Amara, A.; Gamarnik, A. V. Essential Role of Dengue Virus Envelope Protein N Glycosylation at Asparagine-67 during Viral Propagation. JOURNAL OF VIROLOGY, 2007, 7136–7148.
[ 35 ] 35. Steiner, T.; Koellner, G. Hydrogen bonds with pi-acceptors in proteins: frequencies and role in stabilizing local 3D structures. J. Mol. Biol. 2001, 305, 535–557.
[ 36 ] Imai, Y. N.; Inoue, Y.; Yamamoto, Y. Propensities of polar and aromatic amino acids in noncanonical interactions: nonbonded contacts analysis of protein-ligand complexes in crystal structures. J. Med. Chem. 2007, 50, 1189–1196
[ 37 ] Gallivan, J. P.; Dougherty, D. A. A computational study of cation-pi interactions vs salt bridges in aqueous media: implications for protein engineering. J. Am. Chem. Soc. 2000, 122, 870– 874.
[ 38 ] Gallivan, J. P.; Dougherty, D. A. Cation-pi interactions in structural biology. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 9459– 9464.
[ 39 ] Berry, B. W.; Elvekrog, M. M.; Tommos, C. Environmental modulation of protein cation-pi. interactions. J. Am. Chem. Soc. 2007, 129, 5308–5309
[ 40 ] Oh, B.-H.; Ames, G. F.-L.; Kim, S.-H. Structural basis for multiple ligand specificity of the periplasmic lysine-, arginine-, ornithine-binding protein. J. Biol. Chem. 1994, 269, 26323–26330.
[ 41 ] Williamson, D. S.; Borgognoni, J.; Clay, A.; Daniels, Z.; Dokurno, P.; Drysdale, M. J.; Foloppe, N.; Francis, G. L.; Graham, C. J.; Howes, R.; Macias, A. T.; Murray, J. B.; Parsons, R.; Shaw, T.; Surgenor, A. E.; Terry, L.; Wang, Y.; Wood, M.; Massey, A. J. Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design. J. Med. Chem. 2009, 52, 1510–1513.
[ 42 ] Wang, W.; Xi, M.; Duan, X.; Wang, Y.; Kong, F. Delivery of baicalein and paclitaxel using self- assembled nanoparticles: synergistic antitumor effect in vitro and in vivo. International Journal of Nanomedicine. 2015, 10, 3737–3750.