Interaction Model between HRSV G-Protein and Flavonoids

Interaction Model between HRSV G-Protein and Flavonoids

Loading document ...
Page
of
Loading page ...

Author(s)

Author(s): Fátima Pereira de Souza, Mariana Pela Sabgad, Gabriela Campos de Araujo, Haroldo Lima Pimentel Cravo, Thiago Pançonato Salen Teixeira, Valmir Fadel, Deriane Elias Gomes, Marcelo Andres Fossey

Download Full PDF Read Complete Article

523 1108 12-19 Volume 2 - Oct 2013

Abstract

Background: Acute respiratory infections (ARI) are the leading cause of infant mortality in the world, and human respiratory syncytial virus (HRSV) is one of the main agents of ARI. One of the key targets of the adaptive host immune response is the RSV G-protein, which is responsible for attachment to the host cell. There is evidence that compounds such as flavonoids can inhibit viral infection in vitro. With this in mind, the main purpose of this study was to determine, using computational tools, the potential sites for interactions between G-protein and flavonoids. Results: Our study allowed the recognition of an hRSV G-protein model, as well as a model of the interaction with flavonoids. These models were composed, mainly, of -helix and random coil proteins. The docking process showed that molecular interactions are likely to occur. The flavonoid kaempferol-3-O-α-L-arabinopyranosil-(2 → 1)-α-L-apiofuranoside-7-O-α-L-rhamnopyranoside was selected as a candidate inhibitor. The main forces of the interaction were hydrophobic, hydrogen and electrostatic. Conclusions: The model of G-protein is consistent with literature expectations, since it was mostly composed of random coils (highly glycosylated sites) and -helices (lipid regions), which are common in transmembrane proteins. The docking analysis showed that flavonoids interact with G-protein in an important ectodomain region, addressing experimental studies to these sites. The determination of the G-protein structure is of great importance to elucidate the mechanism of viral infectivity, and the results obtained in this study will allow us to propose mechanisms of cellular recognition and to coordinate further experimental studies in order to discover effective inhibitors of attachment proteins.

Keywords

hRSV, G-protein, Molecular docking

References

  1. Bae EA, Han MJ, Lee M, Kim DH. In vitro inhibitory effect of some flavonoids on rotavirus infectivity. Biol Pharm Bull 2000, 23:1122–4
  2. Chivian D, Kim DE, Malmstrom L, Bradley P, Robertson T, Murphy P, Strauss C. E, Bonneau R, Rohl CA, Baker D. Automated prediction of CASP5 structures using the Robetta server. Proteins 2003, 53(Suppl 6):524-533
  3. Esteves A, Parreira R, Venenno T, et al. Molecular epidemiology of HIV type 1 infection in Portugal: high prevalence of non-B subtypes, AIDS Res Hum Retroviruses 2002, 18(5):313-325
  4. Falsey AR, Wash EE. Respiratory syncytial virus infections in adults. Clin Microbiol Rev 2000. 13(3):371-84
  5. Feldman SA, Audet S, Beeler JA. The fusion glycoprotein of human respiratory syncytial virus facilitates virus attachment and infectivity via an interaction with cellular heparan sulfate. J Virol 2000, 74:6442–6447
  6. Friesner RA, Banks JL, Murphy RB, et al. S: Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem 2004, 47:1739–1749
  7. Gorman JJ, Ferguson BL, Speelman D, et al. Determination of the disulfide bond arrangement of human respiratory syncytial virus attachment (G) protein by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Protein Sci 1997, 6:1308-1315
  8. Hall TA. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucl Acids Symp Ser 1999, 41:95-98
  9. Johnson PR, Spriggs MK, Olmsted RA. et al. The G glycoprotein of human respiratory syncytial viruses of subgroups A and B: extensive sequence divergence between antigenically related proteins. Proc Natl Acad Sci USA 1987, 84:5625–5629
  10. Kaul TN, Middleton E Jr, Ogra PL. Antiviral effect of flavonoids on human viruses. J Med Virol 1985, 15:71–9.
  11. Langedijk JP, De Groot BL, Berendsen HJ, et al. Structural homology of the central conserved region of the attachment protein G of respiratory syncytial virus with the fourth subdomain of 55-kDa tumor necrosis factor receptor. Virology 1998, 243:293-302
  12. Laskowski RA, Rullmannn JA, Macarthur MW, et al. AQUA and PROCHECK-NMR: programs for checking the quality of protein structures solved by NMR. J Biomol NMR 1996, 8:477-486
  13. Laurie AT, Jackson RM. Q-SiteFinder: an energy-based method for the prediction of protein-ligand binding sites. Bioinformatics 2005, 21:1908-1916
  14. Lole KS, Bollinger RC, Paranjape RS, et. al. Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination. J Virol 1999, 73(1):152-160
  15. Melero JA, et. al. The soluble form of human respiratory syncytial virus attachment protein differs from the membrane-bound form in its oligomeric state but is still capable of binding to cell surface proteoglycans. J Virol 2004, 78(Suppl l):3524-3532
  16. Miteva MA, Guyon F, Tufféry P. Frog2: Efficient 3D conformation ensemble generator for small compounds. Nucleic Acids Res 2010, 38:622-627
  17. Morris S K, Dzolganovski B, Beyene J, et. al. A meta-analysis of the effect of antibody therapy for the prevention of severe respiratory syncytial virus infection. BMC Infect Dis 2009, 9, n 106
  18. Nakamura M, Itokazu K, Taira K, et al. Genotypic and phylogenetic of the G gene of respiratory syncytial virus isolates in Okinawa, Japan, 2008. Japan J Infect Dis 2009, 62:326-327
  19. Ohuchi M, Ohuchi R, Feldmann A, Klenk HD. Regulation of receptor binding affinity of influenza virus hemagglutinin by its carbohydrate moiety. J Virol 1997, 71:8377–8384
  20. Pavlova S, Hadzhiolova T, Abadjieva P, et. al. Aplication of RT-PCR for diagnosis of respiratory syncytial virus and human metapneumovirus infection in Bulgaria, 2006-7 and 2007-8. Eurosurveillance 2009,14, n. 23
  21. Pencheva T, Lagorce D, Pajeva I, et al. AMMOS: Automated Molecular Mechanics Optimization tool for in silico Screening. BMC Bioinformatics 2008, 9:438
  22. Rost B, Yachdav G, Liu J. The PredictProtein server. Nucleic Acids Res 2004, 32(Web Server issue):W321-6.
  23. Schrödinger; LLC. New York, 2005; http://www.schrodinger.com
  24. Sullender WM. Respiratory syncytial virus genetic and antigenic diversity. Clin Microbiol Rev 2000. 13(1):1-15.
  25. Teng MN, Collins PL. The central conserved cysteine noose of the attachment G protein of human respiratory syncytial virus is not required for efficient viral infection in vitro or in vivo. J Virol 2002, 76:6164-6171
  26. Teng MN, Whitehead SS, Collins PL. Contribution of the respiratory syncytial virus G glycoprotein and its secreted and membrane-bound forms to virus replication in vitro and in vivo. Virology 2001, 289:283–296
  27. Wang HK, Xia Y, Yang ZY, Natschke SL, Lee KH. Recent advances in the discovery and development of flavonoids and their analogues as antitumor and anti-HIV agents. Adv Exp Med Biol 1998, 439:191–225
  28. Wertz GW, Collins PL, Huang Y, et al. Nucleotide sequence of the G protein gene of human respiratory syncytial virus reveals an unusual type of viral membrane protein. Proc Natl Acad Sci U S A 1985, 82(12):4075-4079
  29. Wheeler DL, Barrett T, Benson DA, et. al. Database resources of the National Center for Biotechnology Information. Nucleic Acids Res 2007, 35:5-12
  30. Zimmer M, Danko JP, Pennings SC, et al. Hepatopancreatic endosymbionts in intertidal isopods (Crustacea: Isopoda), and their contribution to digestion. Mar Biol 2001, 138:955–963

Cite this Article:

International Journal of Sciences is Open Access Journal.
This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License.
Author(s) retain the copyrights of this article, though, publication rights are with Alkhaer Publications.

Search Articles

Issue June 2024

Volume 13, June 2024


Table of Contents



World-wide Delivery is FREE

Share this Issue with Friends:


Submit your Paper