Influenza A viruses (IAV) remain a major global health threat due to rapid mutation rates and their ability to cause seasonal epidemics or pandemics. Only three antiviral drugs are currently approved by the FDA and EMA for IAV treatment, and emerging resistance has already rendered earlier therapies ineffective. This highlights the need for alternative strategies. Drug repurposing offers advantages through known safety and pharmacokinetic profiles, while host directed therapies reduce the likelihood of resistance and may provide broad antiviral applicability. However, low molecular weight drugs often show limited bioavailability and systemic side effects, emphasizing the importance of advanced delivery systems such as nanocarriers. This study investigated free and nanocarrier encapsulated host directed compounds 6 bromoindirubin 3'-glycerol oxime ether (6BIGOE) and the PI3K inhibitor pictilisib in lung epithelial cell lines. Cytotoxicity was assessed using LDH assays, MTT assays, and cell counting. Cells infected with various IAV strains were treated with non toxic concentrations, and viral replication was quantified via plaque assays and Western blot analysis. Cytokine and chemokine responses were measured by flow cytometry. To validate the in vitro findings, ex vivo mouse lung slices were infected and treated analogously, followed by plaque assays and histological evaluation. Both compounds showed antiviral activity, and nanocarrier encapsulation preserved efficacy while providing additional benefits. Encapsulated 6BIGOE exhibited reduced toxicity, whereas encapsulated pictilisib showed improved performance ex vivo. Free and encapsulated pictilisib also demonstrated anti inflammatory effects. The ex vivo platform underscored the potential of nanocarrier based delivery for precise therapeutic intervention.
Josefine Schroeder (Thu,) studied this question.