Respiratory viruses, including SARS-CoV-2 and influenza, continue to pose a significant threat to public health, as evidenced by the COVID-19 pandemic. Current systemic antiviral delivery methods such as intravenous infusion or oral administration often result in off-target side effects. To address this issue, we developed a physiologically relevant cell culture model that enables the direct, aerosolised delivery of antivirals to human airway cells grown at the air-liquid interface.
In our proof-of-concept studies, we demonstrated that nebulised antivirals, specifically Paxlovid (Nirmatrelvir-Ritonavir) and Remdesivir, reduced infectious SARS-CoV-2 titre and viral gene copies 48 hours post-infection. Paxlovid (20 µM) was the most effective nebulised therapeutic, producing a greater than 5-fold log10 reduction in viral titre and a 1.4-fold log10 reduction in viral gene copies. Moreover, nebulised Paxlovid treatment reduced the secretion of inflammatory cytokine markers, including Interleukin 4 (IL-4) and Interferon gamma-induced protein 10 (IP-10) compared to virus-alone controls, demonstrating the efficacy of this drug in our model. RNA-Seq analysis was used to further characterise the host-response to SARS-CoV-2 and nebulised therapeutics providing deeper insight into the interaction between drug, virus and host.
This innovative approach offers a more targeted and effective method for antiviral delivery and holds potential for application in treating a wide range of respiratory diseases, including cancer.