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Vaccines 2017, 5(3), 27;

Targeting Host Cell Surface Nucleolin for RSV Therapy: Challenges and Opportunities

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada
Department of Paediatrics, The Hospital for Sick Children, Toronto, ON M5G 1L5, Canada
Lovelace Respiratory Research Institute, Albuquerque, NM 87105, USA
Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON M5G 1L5, Canada
Co-senior authors.
Author to whom correspondence should be addressed.
Academic Editor: Romain Paillot
Received: 9 August 2017 / Revised: 8 September 2017 / Accepted: 14 September 2017 / Published: 19 September 2017
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Nucleolin (NCL) has been reported as a cellular receptor for the human respiratory syncytial virus (RSV). We studied the effects of re-purposing AS1411, an anti-cancer compound that binds cell surface NCL, as a possible novel strategy for RSV therapy in vitro and in vivo. AS1411 was administered to RSV-infected cultures of non-polarized (HEp-2) and polarized (MDCK) epithelial cells and to virus-infected mice and cotton rats. Results of in vitro experiments showed that AS1411, used in micromolar concentrations, was associated with decreases in the number of virus-positive cells. Intranasal administration of AS1411 (50 mg/kg) to RSV-infected mice and cotton rats was associated with partial reductions in lung viral titers, decreased virus-associated airway inflammation, and decreased IL-4/IFN-γ ratios when compared to untreated, infected animals. In conclusion, our findings indicate that therapeutic use of AS1411 has modest effects on RSV replication and host response. While the results underscore the challenges of targeting cell surface NCL as a potential novel strategy for RSV therapy, they also highlight the potential of cell surface NCL as a therapeutic target. View Full-Text
Keywords: nucleolin; RSV; virus; therapy nucleolin; RSV; virus; therapy

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Mastrangelo, P.; Norris, M.J.; Duan, W.; Barrett, E.G.; Moraes, T.J.; Hegele, R.G. Targeting Host Cell Surface Nucleolin for RSV Therapy: Challenges and Opportunities. Vaccines 2017, 5, 27.

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