Reversal of H1N1 influenza virus-induced apoptosis by silver nanoparticles functionalized with amantadine

Amantadine is an antiviral agent, but its clinical use against influenza viruses is limited because of the emergence of drug-resistant viruses. Thus, there is a need for novel anti-influenza agents. The antiviral activity of silver nanoparticles (AgNPs) has attracted increasing attention, with such nanoparticles being employed in biomedical interventions in recent years. Herein, we describe a simple method for surface decoration of AgNPs using amantadine. Co-delivery of AgNPs and amantadine was designed to overcome drug resistance. Compared with AgNPs and AM, amantadine-modified AgNPs (Ag@AM) were shown to inhibit H1N1 infection by CPE, MTT and TEM. Ag@AM also inhibited the activity of hemagglutinin (HA) and neuraminidase (NA). Mechanism investigations revealed that Ag@AM can block H1N1 from infecting host cells and prevent DNA fragmentation, chromatin condensation and activity of caspase-3. Ag@AM inhibited accumulation of reactive oxygen species (ROS) and reversed virus-induced apoptosis by H1N1 virus. Taken together, these findings suggest that Ag@AM is a novel promising efficient virucide for H1N1.