ACE2-functionalized Perfluorocarbon Nanoemulsions Block SARS-CoV-2 D614G Variant and Serve As Oxygen Carriers

Severe COVID-19 is characterized by viral propagation and acute respiratory distress syndrome (ARDS), often necessitating mechanical ventilation with associated complications. We designed a dual-function nanoemulsion to combat both issues simultaneously. Perfluorooctyl bromide (PFOB) nanoemulsions, stabilized by DSPE-PEG 2000 -biotin, were functionalized with recombinant human ACE2-core streptavidin (rhACE2-coreSA) fusion proteins. These ACE2-tethered nanoparticles act as decoys, effectively binding and neutralizing SARS-CoV-2 spike protein pseudotyped lentivirus (D614G variant) in vitro, blocking infection of ACE2-expressing HEK293T cells by up to 99%. Concurrently, the high oxygen solubility of the PFOB core offers significant potential for oxygen delivery. This ACE2-anchored oxygen carrier nanoemulsion represents a promising therapeutic strategy against SARS-CoV-2 and its variants by inhibiting viral entry and mitigating hypoxia.