Biomimetic Copper Nanoparticles Coated with ACE2-Overexpressing Membranes for Selective SARS-CoV-2 Neutralization and Disinfection.

The SARS-CoV-2 spike protein facilitates viral entry into host cells by binding to the human angiotensin-converting enzyme 2 (ACE2) receptor. To exploit this mechanism for therapeutic intervention, a liposome fusion-induced membrane exchange (LIME) strategy to generate biomimetic membrane-integrated liposomes (MILs) from ACE2-overexpressing mammalian cells was developed. Using engineered HeLa cells as a model, MILs have been successfully harvested that retained native surface proteins, including ACE2, as confirmed by immunogold TEM and Western blot analysis. These ACE2-presenting MILs were then coated onto copper nanoparticles (Cu NPs), creating biomimetic Cu@MIL nanostructures with dual functions, including selective viral capture via ACE2-mediated binding and neutralization, as well as potent antiviral activity from Cu NP disinfection. This synergistic platform effectively camouflages the nanomaterial with host-mimetic membranes, conferring targeted viral neutralization and disinfection capabilities. Our findings highlight the potential of Cu@MIL nanoparticles as a decoy-plus antiviral therapeutic for SARS-CoV-2, offering a promising strategy to combat COVID-19 and future pandemics of receptor-specific pathogens.