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

Abstract

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.

Unleashing the potential of cell membrane-based nanoparticles for COVID-19 treatment and vaccination

“…Other similar study reported ACE2-rich human embryonic kidney-293 T cells membrane-derived nanovesicles able to bind SARS-CoV-2 spike in means of biocompetitive inhibition and neutralize the virus, blocking its entry to the cytoplasm of host cells, namely renal tubular epithelial cells [156].…”

“…In order to block the virus entry, cell membrane-coated nanoparticles based on the membrane of human embryonic kidney-239 T cells overexpressing human ACE2 (HEK-293 T-hACE2) have been developed to competitively bind the S1 proteins, thus blocking SARS-CoV-2 binding onto the cell membrane and subsequent entry into its targeted cells. The study showed that these biomimetic nanocarriers adsorbed the SARS-CoV-2 S pseudovirons onto their surface as expected, and indeed blocked viral entry into the cytoplasm, thus disabling virulence [ 157 ].…”

“…The viral spike protein responsible for the pathogenesis of COVID-19 can be divided into S1 and S2 subunits after degradation, where the S1 subunit is responsible for recognizing host receptors, and S2 subunit mediates viral fusion into the cytoplasm [ 157 ]. The S1 binds to ACE2 gaining entry into the cells [ 157 , 158 ] .…”

“…The viral spike protein responsible for the pathogenesis of COVID-19 can be divided into S1 and S2 subunits after degradation, where the S1 subunit is responsible for recognizing host receptors, and S2 subunit mediates viral fusion into the cytoplasm [ 157 ]. The S1 binds to ACE2 gaining entry into the cells [ 157 , 158 ] . In order to block the virus entry, cell membrane-coated nanoparticles based on the membrane of human embryonic kidney-239 T cells overexpressing human ACE2 (HEK-293 T-hACE2) have been developed to competitively bind the S1 proteins, thus blocking SARS-CoV-2 binding onto the cell membrane and subsequent entry into its targeted cells.…”

“…While the biomimetic facet of cell membrane-based nanosystems are known to improve their biocompatibility toward biological systems due to their endogenous cellderived constituents which are the ultimate source of contact with the majority of in vivo environment -either functioning as cell membrane coatings to nanoparticle cores or as cell membrane nanovesicles bearing an aqueous core -it is not exactly clear the potential long-term impact of these nanosystems in humans. The sum of evidence so far has pointed toward their relatively safe profile [19,156]; however, in vitro and in vivo models and the CoV-2 infectivity. The nanosponges were constructed by wrapping polymeric nanoparticle cores with natural cell membranes from target cells, namely lung epithelial cells and macrophages (MΦs).…”