tetano
Editor, Senior Moderator
Nat Commun
. 2022 Jan 20;13(1):405.
doi: 10.1038/s41467-021-27893-2.
Circulating ACE2-expressing extracellular vesicles block broad strains of SARS-CoV-2
Lamiaa El-Shennawy[SUP] #[/SUP][SUP] 1 [/SUP], Andrew D Hoffmann[SUP] #[/SUP][SUP] 1 [/SUP], Nurmaa Khund Dashzeveg[SUP] #[/SUP][SUP] 1 [/SUP], Kathleen M McAndrews[SUP] #[/SUP][SUP] 2 [/SUP], Paul J Mehl[SUP] 3 [/SUP], Daphne Cornish[SUP] 1 [/SUP], Zihao Yu[SUP] 1 [/SUP], Valerie L Tokars[SUP] 1 [/SUP], Vlad Nicolaescu[SUP] 4 [/SUP], Anastasia Tomatsidou[SUP] 4 [/SUP], Chengsheng Mao[SUP] 5 [/SUP], Christopher J Felicelli[SUP] 6 [/SUP], Chia-Feng Tsai[SUP] 7 [/SUP], Carolina Ostiguin[SUP] 3 [/SUP], Yuzhi Jia[SUP] 1 [/SUP], Lin Li[SUP] 8 [/SUP], Kevin Furlong[SUP] 4 [/SUP], Jan Wysocki[SUP] 9 [/SUP], Xin Luo[SUP] 2 [/SUP], Carolina F Ruivo[SUP] 2 [/SUP], Daniel Batlle[SUP] 9 [/SUP], Thomas J Hope[SUP] 10 [/SUP], Yang Shen[SUP] 11 [/SUP], Young Kwang Chae[SUP] 12 [/SUP], Hui Zhang[SUP] 8 [/SUP], Valerie S LeBleu[SUP] 1 2 13 [/SUP], Tujin Shi[SUP] 7 [/SUP], Suchitra Swaminathan[SUP] 3 14 [/SUP], Yuan Luo[SUP] 5 [/SUP], Dominique Missiakas[SUP] 4 [/SUP], Glenn C Randall[SUP] 4 [/SUP], Alexis R Demonbreun[SUP] 1 [/SUP], Michael G Ison[SUP] 15 16 [/SUP], Raghu Kalluri[SUP] 17 18 19 [/SUP], Deyu Fang[SUP] 20 21 [/SUP], Huiping Liu[SUP] 22 23 24 [/SUP]
Affiliations
Abstract
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.
. 2022 Jan 20;13(1):405.
doi: 10.1038/s41467-021-27893-2.
Circulating ACE2-expressing extracellular vesicles block broad strains of SARS-CoV-2
Lamiaa El-Shennawy[SUP] #[/SUP][SUP] 1 [/SUP], Andrew D Hoffmann[SUP] #[/SUP][SUP] 1 [/SUP], Nurmaa Khund Dashzeveg[SUP] #[/SUP][SUP] 1 [/SUP], Kathleen M McAndrews[SUP] #[/SUP][SUP] 2 [/SUP], Paul J Mehl[SUP] 3 [/SUP], Daphne Cornish[SUP] 1 [/SUP], Zihao Yu[SUP] 1 [/SUP], Valerie L Tokars[SUP] 1 [/SUP], Vlad Nicolaescu[SUP] 4 [/SUP], Anastasia Tomatsidou[SUP] 4 [/SUP], Chengsheng Mao[SUP] 5 [/SUP], Christopher J Felicelli[SUP] 6 [/SUP], Chia-Feng Tsai[SUP] 7 [/SUP], Carolina Ostiguin[SUP] 3 [/SUP], Yuzhi Jia[SUP] 1 [/SUP], Lin Li[SUP] 8 [/SUP], Kevin Furlong[SUP] 4 [/SUP], Jan Wysocki[SUP] 9 [/SUP], Xin Luo[SUP] 2 [/SUP], Carolina F Ruivo[SUP] 2 [/SUP], Daniel Batlle[SUP] 9 [/SUP], Thomas J Hope[SUP] 10 [/SUP], Yang Shen[SUP] 11 [/SUP], Young Kwang Chae[SUP] 12 [/SUP], Hui Zhang[SUP] 8 [/SUP], Valerie S LeBleu[SUP] 1 2 13 [/SUP], Tujin Shi[SUP] 7 [/SUP], Suchitra Swaminathan[SUP] 3 14 [/SUP], Yuan Luo[SUP] 5 [/SUP], Dominique Missiakas[SUP] 4 [/SUP], Glenn C Randall[SUP] 4 [/SUP], Alexis R Demonbreun[SUP] 1 [/SUP], Michael G Ison[SUP] 15 16 [/SUP], Raghu Kalluri[SUP] 17 18 19 [/SUP], Deyu Fang[SUP] 20 21 [/SUP], Huiping Liu[SUP] 22 23 24 [/SUP]
Affiliations
- PMID: 35058437
- DOI: 10.1038/s41467-021-27893-2
Abstract
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.