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

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.