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Updated: Feb 22, 2026
Generation, Amplification, and Titration of Recombinant Respiratory Syncytial Viruses
Published on: April 4, 2019
Targeting Host Cell Surface Nucleolin for RSV Therapy: Challenges and Opportunities
Peter Mastrangelo1, Michael J Norris2,3, Wenming Duan4
1Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada. peter.mastrangelo@utoronto.ca.
Abstract:
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.
Insights
Repurposing the anti-cancer drug AS1411 showed modest effects against respiratory syncytial virus (RSV) by targeting nucleolin (NCL). Further research is needed to explore NCL as a therapeutic target for RSV infection.
Area of Science:
- Virology
- Pharmacology
- Immunology
Background:
- Nucleolin (NCL) is identified as a cellular receptor for human respiratory syncytial virus (RSV).
- AS1411 is an anti-cancer compound known to bind cell surface NCL.
Purpose of the Study:
- To investigate the potential of repurposing AS1411 as a novel therapeutic strategy against RSV infection.
- To evaluate the efficacy of AS1411 in vitro and in vivo models of RSV.
Main Methods:
- AS1411 was administered to RSV-infected epithelial cell cultures (HEp-2, MDCK) and RSV-infected mice and cotton rats.
- In vitro assays assessed the reduction in virus-positive cells.
- In vivo studies measured lung viral titers, airway inflammation, and cytokine profiles (IL-4/IFN-γ).
Main Results:
- AS1411 treatment resulted in decreased numbers of RSV-positive cells in vitro at micromolar concentrations.
- Intranasal AS1411 administration (50 mg/kg) led to partial reductions in lung viral titers in mice and cotton rats.
- AS1411 treatment was associated with decreased airway inflammation and altered IL-4/IFN-γ ratios in vivo.
Conclusions:
- Therapeutic use of AS1411 demonstrated modest effects on RSV replication and the host immune response.
- Targeting cell surface NCL presents challenges for RSV therapy but remains a potential strategy.
- These findings highlight the potential of NCL as a therapeutic target for RSV infections.
