Anti-Influenza Activity of 6BIGOE: Improved Pharmacological Profile After Encapsulation in Plga Nanoparticles

Influenza A virus (IAV) infections continue to threaten public health. Current strategies, such as vaccines and antiviral drugs, are limited due to time-consuming development and drug-resistant strains. Therefore, new effective treatments are needed. Here, virus-supportive cellular factors are promising drug targets, and encapsulation of candidate substances in PLGA nanoparticles (NPs) is intended to improve their bioavailability. This study investigates the potential of the indirubin derivative 6BIGOE, a GSK-3β inhibitor, for its potential to regulate IAV replication in vitro. The effects of 6BIGOE-loaded PLGA NPs on cell metabolism were assessed by MTT and LDH assays in A549 and Calu-3 cells. Viral replication and spread were monitored in various IAV-infected cell lines in absence and presence of free and 6BIGOE-loaded PLGA NPs via plaque assays and Western blot analysis. Encapsulation of 6BIGOE in PLGA NPs resulted in reduced negative side effects on cell viability while maintaining antiviral efficacy. Both encapsulated and free 6BIGOE exhibited antiviral activity, potentially through GSK-3β inhibition and disruption of key signaling pathways required for viral replication. The data indicate 6BIGOE, particularly after encapsulation in NPs, as a potential candidate for further investigation and development as an antiviral agent to treat IAV infections.