About: Discovery of drugs to treat cytokine storm-induced cardiac dysfunction using human cardiac organoids

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An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Discovery of drugs to treat cytokine storm-induced cardiac dysfunction using human cardiac organoids
Creator	Hudson, James Bald, Tobias Devilée, Lynn Engwerda, Christian Griffen, Brendan Humphrey, Sean James, David Krumeich, Sophie Macdonald, Kelli Mathieson, Ellen Mehdiabadi, Neda Mills, Richard Porrello, Enzo Quaife-Ryan, Gregory Reynolds, Liam Rj, Patrick Smyth, Mark Titmarsh, Drew Voges, Holly
Source	BioRxiv
abstract	SARS-CoV2 infection leads to cardiac injury and dysfunction in 20-30% of hospitalized patients1 and higher rates of mortality in patients with pre-existing cardiovascular disease2,3. Inflammatory factors released as part of the ‘cytokine storm’ are thought to play a critical role in cardiac dysfunction in severe COVID-19 patients4. Here we use human cardiac organoids combined with high sensitivity phosphoproteomics and single nuclei RNA sequencing to identify inflammatory targets inducing cardiac dysfunction. This state-of-the-art pipeline allowed rapid deconvolution of mechanisms and identification of putative therapeutics. We identify a novel interferon-γ driven BRD4 (bromodomain protein 4)-fibrosis/iNOS axis as a key intracellular mediator of inflammation-induced cardiac dysfunction. This axis is therapeutically targetable using BRD4 inhibitors, which promoted full recovery of function in human cardiac organoids and prevented severe inflammation and death in a cytokine-storm mouse model. The BRD inhibitor INCB054329 was the most efficacious, and is a prime candidate for drug repurposing to attenuate cardiac dysfunction and improve COVID-19 mortality in humans.
has issue date	2020-08-24(xsd:dateTime)
bibo:doi	10.1101/2020.08.23.258574
has license	biorxiv
sha1sum (hex)	81a37d443d2d1b0b87713ba85a6f1bf6267b31b1
schema:url	https://doi.org/10.1101/2020.08.23.258574
resource representing a document's title	Discovery of drugs to treat cytokine storm-induced cardiac dysfunction using human cardiac organoids
schema:publication	bioRxiv
resource representing a document's body	covid:81a37d443d2d1b0b87713ba85a6f1bf6267b31b1#body_text
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