title: A network flow approach to predict protein targets and flavonoid backbones to treat respiratory syncytial virus infection.
abstract: BACKGROUND
  Respiratory syncytial virus (RSV) infection is the major cause of respiratory disease in lower respiratory tract in infants and young children. Attempts to develop effective vaccines or pharmacological treatments to inhibit RSV infection without undesired effects on human health have been unsuccessful. However, RSV infection has been reported to be affected by flavonoids. The mechanisms underlying viral inhibition induced by these compounds are largely unknown, making the development of new drugs difficult.
  
  
  METHODS
  To understand the mechanisms induced by flavonoids to inhibit RSV infection, a systems pharmacology-based study was performed using microarray data from primary culture of human bronchial cells infected by RSV, together with compound-proteomic interaction data available for Homo sapiens.
  
  
  RESULTS
  After an initial evaluation of 26 flavonoids, 5 compounds (resveratrol, quercetin, myricetin, apigenin, and tricetin) were identified through topological analysis of a major chemical-protein (CP) and protein-protein interacting (PPI) network. In a nonclustered form, these flavonoids regulate directly the activity of two protein bottlenecks involved in inflammation and apoptosis.
  
  
  CONCLUSIONS
  Our findings may potentially help uncovering mechanisms of action of early RSV infection and provide chemical backbones and their protein targets in the difficult quest to develop new effective drugs.
authors: Centro Infant, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Avenue Ipiranga 6681, 90619-900 Porto Alegre, RS, Brazil.
authors: José Eduardo
authors: 0000-0002-7729-5738
authors: JE
authors: Vargas
authors: Clinical Research Center, Hospital Israelita Albert Einstein (HIAE), São Paulo, Brazil.
authors: Renato
authors: 0000-0002-6366-0765
authors: R
authors: Puga
authors: Department of Molecular Biology and Biotechnology, Federal University of Rio Grande do Sul (UFRGS), 90619-900 Porto Alegre, RS, Brazil.
authors: Joice
authors: J
authors: de Faria Poloni
authors: Faculty of Informatics, Laboratory for Bioinformatics, Modelling & Simulation of Biosystems, Pontifical Catholic University of Rio Grande do Sul (PUCRS), 90619-900 Porto Alegre, RS, Brazil.
authors: Luis Fernando
authors: LF
authors: Saraiva Macedo Timmers
authors: Centro Infant, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Avenue Ipiranga 6681, 90619-900 Porto Alegre, RS, Brazil.
authors: Barbara Nery
authors: 0000-0002-1995-9874
authors: BN
authors: Porto
authors: Faculty of Informatics, Laboratory for Bioinformatics, Modelling & Simulation of Biosystems, Pontifical Catholic University of Rio Grande do Sul (PUCRS), 90619-900 Porto Alegre, RS, Brazil.
authors: Osmar
authors: 0000-0002-4602-1208
authors: O
authors: Norberto de Souza
authors: Department of Molecular Biology and Biotechnology, Federal University of Rio Grande do Sul (UFRGS), 90619-900 Porto Alegre, RS, Brazil.
authors: Diego
authors: D
authors: Bonatto
authors: Centro Infant, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Avenue Ipiranga 6681, 90619-900 Porto Alegre, RS, Brazil.
authors: Paulo Márcio
authors: PM
authors: Condessa Pitrez
authors: Centro Infant, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Avenue Ipiranga 6681, 90619-900 Porto Alegre, RS, Brazil.
authors: Renato
authors: R
authors: Tetelbom Stein
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage; D003198:Computer Simulation; D055808:Drug Discovery / Q000379:methods; D005419:Flavonoids / Q000008:administration & dosage*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000379:methods*; D025941:Protein Interaction Mapping / Q000379:methods; D011506:Proteins / Q000378:metabolism*; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D005419:Flavonoids; D011506:Proteins