Host Cell-Mimetic Hybrid Nanoparticles as Antiviral Therapeutic Nano-Inhibitors for Influenza Virus

Unpredictable pandemic caused by respiratory virus such as coronavirus disease (COVID-19) poses a great threat to public health due to numerous infections and deaths. Despite the emergence of various diagnostic methods and vaccines, limitations persist in the development of effective antiviral therapeutic agents for promptly addressing newly emerging viruses. Host cell mimetic nanodecoy is an effective strategy to protect against the advancement of infection by neutralizing the virus, impeding its binding and entry into the lung cell membrane, which is the ultimate target of the virus. Herein, we develop an advanced biomimetic nanodecoy capable of trapping the target virus and preventing host cell infection using gold nanoparticles with various topologies and sizes through encapsulating by coating host cell membranes. We fabricated cell membrane-coated Spiky Gold nanoparticles (CM-SGNP) with various topologies, each ranging in size from 50 nm to 120 nm, using a seed-mediated growth method and physical extrusion. The CM-SGNP coated with the Madin-Darby canine kidney cell membrane could efficiently capture Influenza A virus (IAV) virions, providing evidence that the binding event and subsequent infection between host cells and virions will be inhibited. Interestingly, geometry matching between IAV virion and CM-SGNP according to the topology of CM-SGNP suggests that this system has the potential to be customized according to virus type and appearance by controlling the structure of CM-SGNP. Furthermore, CM-SGNP is expected to provide successful delivery and therapeutic effects in-vivo due to its superior biocompatibility characteristics. This system suggests the powerful strategy for treating infectious diseases by combining synthetic and biological materials. It is also the next-generation therapeutic agent that can be widely applied to various virus mutant and newly emerging disease X by setting the ultimate target of the virus to be a nanoinhibitor.