Single-Stranded Oligonucleotide-Mediated Inhibition of Respiratory Syncytial Virus Infection

Area of Science:

• Virology and Molecular Biology
• Antiviral Therapeutics
• Immunology

Background:

• Respiratory syncytial virus (RSV) is a major cause of severe respiratory infections in young children.
• Current therapeutic options for RSV are limited, with no widely available vaccine or antiviral treatment.
• There is an urgent need for novel antiviral strategies to combat RSV.

Purpose of the Study:

• To investigate the potential of non-coding single-stranded oligonucleotides (ssONs) as antiviral agents against RSV.
• To elucidate the mechanism of action of ssONs in inhibiting RSV infection.
• To evaluate the efficacy of ssONs in both in vitro and in vivo models of RSV infection.

Main Methods:

• Utilized a green fluorescent protein (GFP)-expressing RSV to quantify infection in A549 lung epithelial cells.
• Assessed the antiviral activity of ssONs in vitro by measuring viral inhibition and receptor binding competition.
• Employed a luciferase-expressing recombinant RSV to evaluate ssON efficacy in a mouse model and analyzed interferon stimulated gene (ISG) expression.

Main Results:

• ssONs significantly reduced RSV infection in lung epithelial cells in a length-dependent manner.
• Both RNA and DNA ssONs demonstrated antiviral activity by inhibiting viral entry through competition for nucleolin binding.
• ssON treatment effectively blocked RSV infection in mice and upregulated key antiviral ISGs, including Stat1, Stat2, Cxcl10, and Ccl2.

Conclusions:

• Single-stranded oligonucleotides represent a promising class of therapeutic agents for combating RSV infections.
• The mechanism involves inhibiting viral entry via nucleolin receptor competition and modulating the host immune response.
• ssONs offer a potential new avenue for developing effective treatments against RSV.