Browsing by Author "Nicolaescu, Vlad"

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    Circulating ACE2-expressing extracellular vesicles block broad strains of SARS-CoV-2
    (Springer Nature, 2022) El-Shennawy, Lamiaa; Hoffmann, Andrew D.; Dashzeveg, Nurmaa Khund; McAndrews, Kathleen M.; Mehl, Paul J.; Cornish, Daphne; Yu, Zihao; Tokars, Valerie L.; Nicolaescu, Vlad; Tomatsidou, Anastasia; Mao, Chengsheng; Felicelli, Christopher J.; Tsai, Chia-Feng; Ostiguin, Carolina; Jia, Yuzhi; Li, Lin; Furlong, Kevin; Wysocki, Jan; Luo, Xin; Ruivo, Carolina F.; Batlle, Daniel; Hope, Thomas J.; Shen, Yang; Chae, Young Kwang; Zhang, Hui; LeBleu, Valerie S.; Shi, Tujin; Swaminathan, Suchitra; Luo, Yuan; Missiakas, Dominique; Randall, Glenn C.; Demonbreun, Alexis R.; Ison, Michael G.; Kalluri, Raghu; Fang, Deyu; Liu, Huiping
    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.