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BioMed Research International
Volume 2015, Article ID 301635, 9 pages
http://dx.doi.org/10.1155/2015/301635
Research Article

A Network Flow Approach to Predict Protein Targets and Flavonoid Backbones to Treat Respiratory Syncytial Virus Infection

1Centro Infant, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Avenue Ipiranga 6681, 90619-900 Porto Alegre, RS, Brazil
2Clinical Research Center, Hospital Israelita Albert Einstein (HIAE), São Paulo, Brazil
3Department of Molecular Biology and Biotechnology, Federal University of Rio Grande do Sul (UFRGS), 90619-900 Porto Alegre, RS, Brazil
4Faculty of Informatics, Laboratory for Bioinformatics, Modelling & Simulation of Biosystems, Pontifical Catholic University of Rio Grande do Sul (PUCRS), 90619-900 Porto Alegre, RS, Brazil

Received 26 July 2014; Accepted 11 September 2014

Academic Editor: Jiangning Song

Copyright © 2015 José Eduardo Vargas et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.