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, 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-PEG₂₀₀₀-biotin, were functionalized with recombinant human angiotensin-converting enzyme 2 (ACE2)-core streptavidin fusion proteins. These ACE2-tethered nanoparticles act as decoys, effectively binding and neutralizing SARS-CoV-2 spike protein pseudotyped lentivirus (D614G variant)<i>in vitro</i>, 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.