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Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Nat+Commun 2022 ; 13 (1): 405 Nephropedia Template TP
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Circulating ACE2-expressing extracellular vesicles block broad strains of SARS-CoV-2 #MMPMID35058437
El-Shennawy L; Hoffmann AD; Dashzeveg NK; McAndrews KM; Mehl PJ; Cornish D; Yu Z; Tokars VL; Nicolaescu V; Tomatsidou A; Mao C; Felicelli CJ; Tsai CF; Ostiguin C; Jia Y; Li L; Furlong K; Wysocki J; Luo X; Ruivo CF; Batlle D; Hope TJ; Shen Y; Chae YK; Zhang H; LeBleu VS; Shi T; Swaminathan S; Luo Y; Missiakas D; Randall GC; Demonbreun AR; Ison MG; Kalluri R; Fang D; Liu H
Nat Commun 2022[Jan]; 13 (1): 405 PMID35058437show ga
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 (alpha, beta, and delta) 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.