PXD077914

PXD077914 is an original dataset announced via ProteomeXchange.

Title	Efferocytosis of apoptotic bodies drives SARS-CoV-2 infection and macrophage inflammation
Description	SARS-CoV-2 typically utilises host receptor angiotensin-converting enzyme 2 (ACE2) for viral entry. Despite low ACE2 expression, monocyte-derived macrophages, the predominant lung macrophage during severe COVID-19, are often found with SARS-CoV-2 in infected lungs. As macrophage inflammation and cytokine storm are key immunopathological events that drive severe COVID-19, insights into mechanisms underlying viral entry into macrophages are critical to devise novel COVID-19 therapies. Mounting evidence supports that COVID-19 pathogenesis is associated with apoptosis, a type of programmed cell death which releases large extracellular vesicles called apoptotic bodies (ApoBDs). Here, we showed that ApoBDs from SARS-CoV-2-infected cells carried infectious virions. Macrophages efferocytosed these ApoBDs, enabling SARS-CoV-2 entry and pro-inflammatory responses including inflammasome and NF-κB signalling. To demonstrate targetability of this ApoBD efferocytosis-mediated viral entry, we screened for inhibitors of SARS-CoV-2-induced ApoBD formation and identified T-type voltage-gated calcium channel (T-channel) blockers. Mechanistically, T-channel blockers impaired the extracellular calcium influxes required for ApoBD biogenesis. Importantly, blockade of ApoBD formation by T-channel blockers were able to limit cell-to-cell viral transmission, macrophage inflammation and lung immunopathology. Our discovery reveals a novel route for SARS-CoV-2 infection and cytokine storm induction, expanding our understanding of COVID-19 pathogenesis and demonstrating a therapeutic target for infectious diseases.
HostingRepository	PRIDE
AnnounceDate	2026-09-07
AnnouncementXML	Submission_2026-09-07_04:21:36.857.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pamali Fonseka
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2026-05-01 05:59:00	ID requested
⏵ 1	2026-09-07 04:21:37	announced

10.1038/s41467-026-74363-8;

Phan TK, Sheerin D, Shi B, Chua NK, Gummadi S, Dayton M, Mackiewicz L, Maluenda A, Ozkocak DC, Atkin-Smith GK, Peton N, Ang CS, Audi O, Thinh Le Q, Tran TU, Tu TM, Tixeira R, Ashdown GW, Davidson KC, Fonseka P, Feltham R, Doerflinger M, Hulett MD, Coussens AK, Poon IKH, Efferocytosis of apoptotic bodies drives SARS-CoV-2 infection and macrophage inflammation. Nat Commun, 17(1):(2026) [pubmed]

submitter keyword: COVID-19, apoptotic bodies, macrophage, inflammation, SARS-CoV-2, apoptosis, infection, efferocytosis

Thanh Kha Phan
contact affiliation	Department of Biochemistry and Chemistry, Research Centre for Extracellular Vesicles, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia
contact email	Kha.Phan@latrobe.edu.au
lab head
Pamali Fonseka
contact affiliation	La Trobe University
contact email	p.fonseka@latrobe.edu.au
dataset submitter

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.pride.ebi.ac.uk/pride/data/archive/2026/09/PXD077914

PRIDE project URI

• PRIDE
  1. PXD077914
     1. Label: PRIDE project
     2. Name: Efferocytosis of apoptotic bodies drives SARS-CoV-2 infection and macrophage inflammation