A High-Content Screen for Mucin-1-Reducing Compounds Identifies Fostamatinib as a Candidate for Rapid Repurposing for Acute Lung Injury.

ALI ARDS COVID-19 MUC1 SARS-CoV-2 acute lung injury acute respiratory distress syndrome drug repurposing fostamatinib

Journal

Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894

Informations de publication

Date de publication:
17 11 2020
Historique:
received: 29 06 2020
revised: 23 09 2020
accepted: 13 10 2020
entrez: 9 12 2020
pubmed: 10 12 2020
medline: 10 12 2020
Statut: epublish

Résumé

Drug repurposing has the advantage of identifying potential treatments on a shortened timescale. In response to the pandemic spread of SARS-CoV-2, we took advantage of a high-content screen of 3,713 compounds at different stages of clinical development to identify FDA-approved compounds that reduce mucin-1 (MUC1) protein abundance. Elevated MUC1 levels predict the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) and correlate with poor clinical outcomes. Our screen identifies fostamatinib (R788), an inhibitor of spleen tyrosine kinase (SYK) approved for the treatment of chronic immune thrombocytopenia, as a repurposing candidate for the treatment of ALI.

Identifiants

DOI: 10.1016/j.xcrm.2020.100137 PMID: 33294858 PMC: PMC7691435
pubmed: 33294858
doi: 10.1016/j.xcrm.2020.100137
pii: S2666-3791(20)30181-6
pmc: PMC7691435
doi:

Types de publication

Journal Article

Langues

eng

Pagination

100137

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI042269
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI148161
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007753
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007627
Pays : United States

Commentaires et corrections

Type : UpdateOf

Informations de copyright

© 2020 The Author(s).

Déclaration de conflit d'intérêts

F.W.K.T. has received research project grants from and has consultancy agreements with Rigel Pharmaceuticals, and is the chief investigator of an international clinical trial of a SYK inhibitor in IgA nephropathy (ClinicalTrials.gov NCT02112838), funded by Rigel Pharmaceuticals.

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Auteurs

Maria Kost-Alimova (M)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Eriene-Heidi Sidhom (EH)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Abhigyan Satyam (A)

Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.

Brian T Chamberlain (BT)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Moran Dvela-Levitt (M)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Michelle Melanson (M)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Seth L Alper (SL)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.

Jean Santos (J)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Juan Gutierrez (J)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Ayshwarya Subramanian (A)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Patrick J Byrne (PJ)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Elizabeth Grinkevich (E)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Estefanía Reyes-Bricio (E)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Choah Kim (C)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Abbe R Clark (AR)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Andrew J B Watts (AJB)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Rebecca Thompson (R)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Jamie Marshall (J)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Juan Lorenzo Pablo (JL)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Juliana Coraor (J)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Julie Roignot (J)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Katherine A Vernon (KA)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Keith Keller (K)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Alissa Campbell (A)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Maheswarareddy Emani (M)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Matthew Racette (M)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Silvana Bazua-Valenti (S)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Valeria Padovano (V)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Astrid Weins (A)

Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Stephen P McAdoo (SP)

Department of Immunology and Inflammation, Imperial College, Hammersmith Hospital, London, UK.

Frederick W K Tam (FWK)

Department of Immunology and Inflammation, Imperial College, Hammersmith Hospital, London, UK.

Luciene Ronco (L)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Florence Wagner (F)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

George C Tsokos (GC)

Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.

Jillian L Shaw (JL)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Anna Greka (A)

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Classifications MeSH