PXD029662

PXD029662 is an original dataset announced via ProteomeXchange.

Title	Circulating ACE2-expressing Extracellular Vesicles as an Innate Antiviral Response and A Decoy Therapy to Block Broad Strains of SARS-CoV-2
Description	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)has caused the pandemic of the coronavirus induced disease 2019 (COVID-19) with 216 million cases and 4.5 million deathsas of September 2021.Thathas been exacerbated by mutated variants such as α, β, and with high infection rates and increased breakthroughs,resulting in vaccine inefficiencies and resistance to therapeutic monoclonal antibodies. Itremains urgentto identify novel therapeutics against broad strains of SARS-CoV-2 andfuture emerging corona viruses to protect the immune-compromised, unvaccinated, and even vaccinatedalikefrom evolvinginfectious diseases. Onebig question is whether we can harness power from human antiviral immunity for such broad therapeutic development. Wild-type SARS-CoV-2 and its variants infect human and other host cellsvia the entry receptor angiotensin-converting enzyme 2 (ACE2),triggeringinnate and adaptive immune responses. Herein, we reportan increase in circulating extracellular vesicles (EVs) that express ACE2(evACE2)in plasma ofboth acuteand convalescent COVID-19 patientsas part of innate antiviral responseassociatedwith severe pathogenesis. Furthermore, evACE2 isolated from both human plasma and engineered EV-producing cell lines neutralizes SARS-CoV-2 infection by competingwith cellular ACE2.Notably,evACE2 blocksthe binding of the viral spike (S)protein RBD to ACE2+cells ata135-fold higherpotencythan vesicle-free recombinant human ACE2 (rhACE2). Furthermore, evACE2 preventscellinfections by both pseudotyped and authentic SARS-CoV-2at a 60-to 80-fold higher efficacy than rhACE2; and itprotectsthe hACE2 mice from SARS-CoV-2-induced lung injury and mortality. More importantly, evACE2 inhibitsthe infection of SARS-CoV-2 variants (α, β,and δ)with an equal or even higherpotencythan forthe WT strain, supportingevACE2 as a broad-spectrum antiviral mechanismfor therapeutic developmentto block the infection of existing and future coronaviruses that use ACE2 as a receptor.
HostingRepository	jPOST
AnnounceDate	2021-12-10
AnnouncementXML	Submission_2022-11-21_08:25:38.066.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Chia-Feng Tsai
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	L-methionine sulfoxide; alpha-amino acetylated residue; S-carboxamidomethyl-L-cysteine
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-10 15:36:47	ID requested
1	2021-12-10 11:43:04	announced
2	2022-09-18 02:26:52	announced	2022-09-18: Updated FTP location.
⏵ 3	2022-11-21 08:25:38	announced	2022-11-22: Updated PubMed.

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, Circulating ACE2-expressing extracellular vesicles block broad strains of SARS-CoV-2. Nat Commun, 13(1):405(2022) [pubmed]

submitter keyword: ACE2, SARS-CoV-2

Huiping Liu
lab head
Chia-Feng Tsai
contact affiliation	Pacific Northwest National Laboratory
dataset submitter

jPOST dataset URI

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.jpostdb.org/JPST001379/