bafilomycin-a and Influenza--Human

Influenza virus infections are a major public health concern worldwide. Conventional treatments against the disease are designed to target viral proteins. However, the emergence of viral variants carrying drug-resistant mutations can outpace the development of pathogen-targeting antivirals. Diphyllin and bafilomycin are potent vacuolar ATPase (V-ATPase) inhibitors previously shown to have broad-spectrum antiviral activity. However, their poor water solubility and potential off-target effect limit their clinical application.. In this study, we report that nanoparticle encapsulation of diphyllin and bafilomycin improves the drugs' anti-influenza applicability.. Using PEG-PLGA diblock copolymers, sub-200 nm diphyllin and bafilomycin nanoparticles were prepared, with encapsulation efficiency of 42% and 100%, respectively. The drug-loaded nanoparticles have sustained drug release kinetics beyond 72 hours and facilitate intracellular drug delivery to two different influenza virus-permissive cell lines. As compared to free drugs, the nanoparticulate V-ATPase inhibitors exhibited lower cytotoxicity and greater. These results demonstrate the potential of the nanoparticulate V-ATPase inhibitors for host-targeted treatment against influenza.

Topics: Animals; Antiviral Agents; Benzodioxoles; Cell Line; Dogs; Drug Liberation; Enzyme Inhibitors; Humans; Influenza, Human; Inhibitory Concentration 50; Kinetics; Lignans; Macrolides; Mice; Nanoparticles; Orthomyxoviridae; Orthomyxoviridae Infections; Vacuolar Proton-Translocating ATPases; Viral Proteins; Virus Replication