Membrane Nanoparticles Derived from ACE2-Rich Cells Block SARS-CoV‑2 Infection

The
ongoing COVID-19 pandemic worldwide necessitates the development
of therapeutics against SARS-CoV-2. ACE2 is the main receptor of SARS-CoV-2
S1 and mediates viral entry into host cells. Herein, membrane nanoparticles
(NPs) prepared from ACE2-rich cells were discovered to have potent
capacity to block SARS-CoV-2 infection. The membranes of human embryonic
kidney-239T cells highly expressing ACE2 were applied to prepare NPs
using an extrusion method. The nanomaterials, termed ACE2-NPs, contained
265.1 ng mg–1 ACE2 on the surface and acted as baits
to trap S1 in a dose-dependent manner, resulting in reduced recruitment
of the viral ligand to HK-2 human renal tubular epithelial cells.
Aside from affecting receptor recongnition, S1 translocated to the
cytoplasm and induced apoptosis by reducing optic atrophy 1 expression
and increasing cytochrome c release, which was also inhibited by ACE2-NPs.
Further investigations revealed that ACE2-NPs efficiently suppressed
SARS-CoV-2 S pseudovirions entry into host cells and blocked viral
infection in vitro and in vivo.
This study characterizes easy-to-produce memrbane nanoantagonists
of SARS-CoV-2 that enrich the existing antiviral arsenal and provide
possibilities for COVID-19 treatment.