Circulating ACE2-expressing extracellular vesicles block broad strains of SARS-CoV-2

Area of Science:

• Virology
• Immunology
• Biochemistry

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, with evolving variants posing a continuous threat.
• SARS-CoV-2 infects host cells using the angiotensin-converting enzyme 2 (ACE2) receptor.
• Developing broad-spectrum antiviral strategies targeting ACE2 is crucial.

Purpose of the Study:

• To investigate extracellular vesicles expressing ACE2 (evACE2) as a potential therapeutic for SARS-CoV-2 infection.
• To evaluate the neutralizing capacity and potency of evACE2 against SARS-CoV-2 and its variants.

Main Methods:

• Quantification of evACE2 in plasma from COVID-19 patients.
• Isolation and characterization of evACE2 from human plasma and cells.
• In vitro assays to assess evACE2's ability to block viral entry and neutralize SARS-CoV-2 (wildtype and variants).
• In vivo studies using hACE2 transgenic mice to evaluate evACE2's therapeutic efficacy.

Main Results:

• Elevated levels of evACE2 were observed in the plasma of COVID-19 patients, correlating with severe disease.
• Isolated evACE2 demonstrated potent neutralization of SARS-CoV-2 infection, outperforming vesicle-free recombinant ACE2 (rhACE2).
• evACE2 exhibited significant efficacy against SARS-CoV-2 variants (α, β, δ), suggesting a broad-spectrum mechanism.

Conclusions:

• Circulating evACE2 represents a potential biomarker for COVID-19 severity.
• evACE2 shows promise as a broad-spectrum antiviral therapeutic agent against SARS-CoV-2 and potentially other ACE2-dependent coronaviruses.
• The enhanced potency and efficacy of evACE2 warrant further investigation for clinical development.