Pan-antiviral effects of RIG-I agonist (RIG-101) against respiratory syncytial virus and human rhinovirus in nasal epithelium in vitro and mice in vivo

<bold>Background:</bold> Human rhinovirus (HRV) and respiratory syncytial virus (RSV), but not limited to, are known to cause severe diseases in patients with chronic respiratory diseases, such as asthma and COPD. However, antivirals and vaccination are virus specific, and the induction of host immunity is an attractive option for broad spectrum antivirals. <bold>Aim:</bold> To assess the antiviral effects of a RIG-I agonist (RIG101 nanoemulsion: RIGImmune Inc.) against HRV16 and RSVA2 infection in air liquid interface cultured nasal epithelium in vitro and RSV in mice in vivo. <bold>Methods:</bold> Human nasal epithelium (Epithelix Sarl) was treated with RIG-101 on Day -4 and -1 (or Day -1 and -1hr) apically prior to HRV or RSV infection. Apical wash was collected daily to analyse viral load and cytokine release. For in vivo, RIG-101 administered intranasally to mice on Day-4 and -1 prior to the intranasal RSV challenge. Viral load and inflammatory cells infiltration were determined in nasal/lung tissue and lavage on day 5 post infection. <bold>Results:</bold> RIG-101 strongly induced CXCL10, as a surrogate marker of antiviral interferon production and significantly reduced viral load 24-48hr post HRV or RSV inoculation in nasal epithelium. While intranasal RIG-101 treatment also significantly reduced viral load and prevented neutrophil accumulation in nasal/lung tissue or lavage. The antiviral effect was comparable or superior to intranasal ribavirin. <bold>Conclusion:</bold> Prophylactic treatment of RIG-101 nanoemulsion demonstrate potent antiviral activities against HRV and RSV, suggesting that topical RIG101 delivered to nasal tract can induce sterilising immunity.