PXD037615

PXD037615 is an original dataset announced via ProteomeXchange.

Title	Rational treatment strategies for SARS-CoV-2 derived from human iPSC models
Description	SARS-CoV-2 infects the respiratory tract, primarily causing pulmonary disease and cardiac complications described in many COVID-19 cases. To elucidate the molecular mechanisms of SARS-CoV-2 infection in the lung and heart, we conducted paired experiments in human stem cell-derived lung alveolar type II (AT2) epithelial cell and cardiac cultures, that were productively infected with SARS-CoV-2. SARS-CoV-2 variants of concern infected heart and lung cells with comparable efficiency. With CRISPR-Cas9 mediated knock-out of ACE2, we demonstrated that angiotensin converting enzyme 2 (ACE2) was essential for SARS-CoV-2 infection of both cell types. Further processing of the spike protein in lung cells required TMPRSS2 while infection of cardiac cells was achieved through the endosomal pathway and Cathepsin L. Host responses were significantly different, with a strong interferon response following infection in cardiac cells but not in lung AT2 cells. Transcriptome profiling and phosphoproteomics demonstrated that response to SARS-CoV-2 depended strongly on the cell type. We evaluated antiviral drugs that are approved for treatment of COVID-19, drugs that showed antiviral activity in vitro but were not found to be effective in clinical trials or are still under investigation and drugs targeting molecules identified in our molecular datasets in both cell types. We identified several antiviral compounds with distinct antiviral and toxicity profiles in lung AT2 and cardiac cells, highlighting the importance of using several relevant cell types for evaluation of antiviral drugs. Our data provide new insights into rational drug combinations for effective treatment of a virus that affects multiple organ systems.
HostingRepository	PRIDE
AnnounceDate	2023-05-08
AnnouncementXML	Submission_2023-05-07_23:13:10.559.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	SeanHumphrey
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-20 13:27:34	ID requested
⏵ 1	2023-05-07 23:13:10	announced

Dataset with its publication pending

ProteomeXchange project tag: Sars-cov-2, Covid-19

submitter keyword: SARS-CoV-2, heart, COVID, lung, stem cells, pluripotent

SeanHumphrey
contact affiliation	Murdoch Children's Research Institute, Melbourne, Australia
contact email	sean.humphrey@mcri.edu.au
lab head
SeanHumphrey
contact affiliation	Murdoch Children's Research Institute
contact email	sean.j.humphrey@gmail.com
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/2023/05/PXD037615

PRIDE project URI

• PRIDE
  1. PXD037615
     1. Label: PRIDE project
     2. Name: Rational treatment strategies for SARS-CoV-2 derived from human iPSC models