PXD060880

PXD060880 is an original dataset announced via ProteomeXchange.

Title	SARS-CoV-2 non-spike structural proteins hijack mucosa epithelial cell fate
Description	COVID-19 patients readily present with severe epithelial damages such as ulceration, erosions, loss of tissue repair etc. in multiple organs. Mucosa aligning such as lung alveoli, gastrointestinal tract, oral cavity are primary targets of SARS-CoV-2 infection. The infected epithelium triggers dysregulated immune response that further damage tissues and organs. Increasing evidence suggest that the SARS-CoV-2 virus can cause direct damages on epithelial cells and fibroblasts. Here we report that the COVID-19 patient mucosa epithelium can undergo cellular dedifferentiation before any pathological features being observed. SARS-CoV-2 non-spike structural proteins, particularly the Envelope protein can rapidly induce epithelial dedifferentiation, micronuclei, cell cycle arrest to G1 phase and apoptosis. The protein can also severely affect progenitor cell stratification programme. Mechanistically, we have identified a unique molecular: Calponin 2 (CNN2) as the downstream effector of non-spike structural proteins. CNN2 was elevated in the COVID-19 patients’ epitheliums. Down regulating CNN2 could suppress epithelial cell apoptosis and restore differentiation programmes. The elevated CNN2 was under the negative control of Glis2, a transcriptional factor, which was associated with the failure of ciliary dynamics in the epithelial cells. We therefore propose a novel “double hijack” concept of how SARS-CoV-2 damages the mucosa epithelium integrity, with new therapeutic targets of COVID-19 treatment.
HostingRepository	PRIDE
AnnounceDate	2026-04-06
AnnouncementXML	Submission_2026-04-05_16:55:52.080.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vikram Sharma
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-17 08:14:18	ID requested
⏵ 1	2026-04-05 16:55:53	announced

10.1038/s41419-026-08611-6;

Gao Y, Souza LL, Kang HS, Li Z, Hernandez-Guerrero JC, Alves FA, Zhang W, Sharma V, Hanks S, Yu J, Tredwin C, Jetten AM, Soares CD, Hu B, SARS-CoV-2 nonspike structural proteins hijack mucosa epithelial cell fate. Cell Death Dis, 17(1):(2026) [pubmed]

submitter keyword: COVID-19, Spike Protein, SARS-CoV-2, Proteomics

Vikram Sharma
contact affiliation	School of Biomedical Sciences, University of Plymouth
contact email	vikram.sharma@plymouth.ac.uk
lab head
Vikram Sharma
contact affiliation	Plymouth University Peninsula Schools of Medicine and Dentistry
contact email	vikram.sharma@plymouth.ac.uk
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/2026/04/PXD060880

PRIDE project URI

• PRIDE
  1. PXD060880
     1. Label: PRIDE project
     2. Name: SARS-CoV-2 non-spike structural proteins hijack mucosa epithelial cell fate