Effects of an anti-viral interferon booster, RIG-I agonist (RIG-101), on influenza infection in vitro and in vivo

<bold>Background:</bold> Respiratory virus infections, notably influenza and SARS-CoV2, pose significant health, economic, and social challenges globally. With limited efficacy of direct-antiviral agents and vaccines, boosting innate immunity is emerging as a promising strategy for prevention of viral infection and both pandemic and seasonal endemic preparedness. <bold>Aim:</bold> To assess the antiviral effects of a RIG-I agonist (RIG-101 nanoemulsion: RIGImmune Inc.) against influenza infection (H1N1:PR8) in air liquid interface cultured human nasal epithelium in vitro and mice in vivo. <bold>Methods:</bold> Nasal epithelium (Epithelix Sarl) was treated with RIG-101 on Day -4 and -1 prior to virus infection. Apical wash was collected daily to analyse viral load and cytokine release. For in vivo, RIG-101 was administered intranasally to mice on Day-3, Day-1 and -1hr prior to the intranasal virus challenge. Viral load and inflammatory cells infiltration were determined in nasal/lung tissue and lavage on day 1 and 5 post infection. <bold>Results:</bold> RIG-101 strongly induced CXCL10, a surrogate marker of antiviral interferon production, and significantly reduced viral load 48hr post virus inoculation in vitro. Intranasal RIG-101 treatment significantly reduced viral load in nasal and lung tissue and prevented neutrophil accumulation in nasal lavage. The antiviral effect was comparable or superior to oseltamivir. <bold>Conclusion:</bold> RIG-101 was found to show significant induction of interferon signalling, and potent antiviral effects against influenza in vitro and in vivo. This suggests that topical prophylactic treatment of RIG-101 has potential to show viral prevention efficacy against influenza infection.