(417d) Inhibition of Sars-Cov-2 Spike Protein Pseudotyped Virus Infection Using ACE2-Tethered Micro/Nanoparticles

Coronavirus disease 2019 (COVID-19) has caused a global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme 2 receptor (ACE2) is a key receptor for SARS-CoV-2 to infect the host. The binding between spike protein (S) and ACE2 facilitates the entrance of SARS-CoV-2 to the host cell. SARS-CoV-2 is constantly nutating into new variants that cause high infection rate. The development of prophylactic and therapeutics approaches remains needed to fight against mutated SARS-CoV-2 variants. In this study, ACE2-streptavidin fusion protein expressed by recombinant DNA technology was anchored on biotinylated fluorescent polystyrene particles of various sizes ranging from 0.15 to 5 µm. ACE2-tethered micro/nanoparticles were shown to block spike protein pseudotyped lentivirus entry to ACE2-expressing HEK293T cells. interfere with viral attachment, viral entry, and ensuing infection. Compared to ACE2 in soluble form, 5-µm particles immobilized with ACE2 were more efficiently interfere with viral attachment, entry, and its ensuing infection. Furthermore, ACE2-tethered particles inhibited the infection of SARS-CoV-2 D614G variant up to 90%. Our results showed that particles functionalized with ACE2 could be used as efficient decoys to block the infection of SARS-CoV-2 strains.