Elucidating the neuropathophysiology of COVID-19 using quantum dot biomimetics of SARS-CoV-2

Quantum dots were encapsulated in polymeric phospholipid micelles conjugated to multiple ligands of SARS-CoV-2 spike protein to form fluorescent biomimetic nanoparticles for SARS-CoV-2 (COVID-QDs). Phosphatidylethanolamine-polyethylene glycol (PE:PEG) was appended with bis(4-methylphenyl)sulfone to form PE:PEG:bis-sulfone and self-assembled into micelles around CdSe/CdS core/shell quantum dots via thin-film rehydration. The introduction of the bis-sulfone group the surface of the micelle-encapsulated quantum dots provides multiple sites for conjugation to his-tagged SARS-CoV-2 spike protein via a bisalkylation mechanism. Based on the eluted unconjugated fraction, we estimate that an average of seven spike proteins are conjugated per COVID-QD. We treated an in-vitro model system for the neurovascular unit (NVU) with these COVID-QD constructs to investigate the COVID-QDs, and by proxy SARS-CoV-2, may modulate the NVU leading to the COVID-19 associated neuropathophysiology.