The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the pandemic of the coronavirus induced disease 2019 (COVID-19) with evolving variants of concern. It remains urgent to identify novel approaches against broad strains of SARS-CoV-2, which infect host cells via the entry receptor angiotensin-converting enzyme 2 (ACE2). Herein, we report an increase in circulating extracellular vesicles (EVs) that express ACE2 (evACE2) in plasma of COVID-19 patients, which levels are associated with severe pathogenesis. Importantly, evACE2 isolated from human plasma or cells neutralizes SARS-CoV-2 infection by competing with cellular ACE2. Compared to vesicle-free recombinant human ACE2 (rhACE2), evACE2 shows a 135-fold higher potency in blocking the binding of the viral spike protein RBD, and a 60- to 80-fold higher efficacy in preventing infections by both pseudotyped and authentic SARS-CoV-2. Consistently, evACE2 protects the hACE2 transgenic mice from SARS-CoV-2-induced lung injury and mortality. Furthermore, evACE2 inhibits the infection of SARS-CoV-2 variants (α, β, and δ) with equal or higher potency than for the wildtype strain, supporting a broad-spectrum antiviral mechanism of evACE2 for therapeutic development to block the infection of existing and future coronaviruses that use the ACE2 receptor. El-Shennawy et al. report that ACE2 + circulating extracellular vesicles (evACE2) are associated with COVID-19 severity and that evACE2 inhibits the infection of SARS-CoV-2 variants of concern at a higher efficacy than soluble ACE2.
【저자키워드】 SARS-CoV-2, viral infection, biologics, 【초록키워드】 COVID-19, Efficacy, ACE2, coronavirus, pandemic, Pathogenesis, Mortality, Antiviral, SARS-COV-2 infection, severity, SARS-CoV-2 variant, Infection, COVID-19 severity, variants of concern, ACE2 receptor, Lung injury, severe acute respiratory syndrome Coronavirus, angiotensin-converting enzyme 2, Spike protein, hACE2, human ACE2, Viral, SARS-CoV-2 variants, RBD, therapeutic, plasma, extracellular vesicle, respiratory, disease, mechanism, COVID-19 patients, binding, soluble ACE2, cellular, Human plasma, angiotensin, strain, host cells, host cell, viral spike protein, acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, transgenic mice, entry receptor, wildtype, circulating, Express, pseudotyped, infect, EVs, Cell, neutralize, PROTECT, identify, caused, approach, inhibit, coronavirus, increase in, competing, preventing infection, with COVID-19, 【제목키워드】 extracellular vesicle, strain,