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

Area of Science:

• Nanomedicine
• Virology
• Cell Biology

Background:

• The COVID-19 pandemic urgently requires new therapeutics targeting SARS-CoV-2.
• Angiotensin-converting enzyme 2 (ACE2) is the primary receptor for SARS-CoV-2 S1 subunit, mediating viral entry.
• Developing effective antiviral strategies remains critical.

Purpose of the Study:

• To investigate the potential of ACE2-rich membrane nanoparticles (ACE2-NPs) as a therapeutic strategy against SARS-CoV-2.
• To characterize the mechanism by which ACE2-NPs inhibit viral infection.

Main Methods:

• Preparation of membrane nanoparticles (NPs) from ACE2-overexpressing human embryonic kidney-293T cells using extrusion.
• Quantification of surface ACE2 on ACE2-NPs.
• Assessing the capacity of ACE2-NPs to bind S1 subunit and inhibit viral entry into HK-2 cells.
• Evaluating the effect of ACE2-NPs on S1-induced apoptosis.
• Testing the efficacy of ACE2-NPs against SARS-CoV-2 pseudovirions in vitro and in vivo.

Main Results:

• ACE2-NPs were successfully prepared with high surface ACE2 density (265.1 ng mg^-1).
• ACE2-NPs effectively trapped the SARS-CoV-2 S1 subunit in a dose-dependent manner, reducing viral ligand binding to host cells.
• ACE2-NPs inhibited S1-induced apoptosis by modulating optic atrophy 1 expression and cytochrome c release.
• ACE2-NPs demonstrated significant suppression of SARS-CoV-2 pseudovirions entry in vitro and blocked viral infection in vivo.

Conclusions:

• Easy-to-produce ACE2-NPs act as potent nanoantagonists against SARS-CoV-2.
• ACE2-NPs offer a promising therapeutic avenue for COVID-19 treatment by blocking viral entry and downstream cellular damage.
• This study contributes novel membrane-based nanomaterials to the antiviral arsenal.