Disulfiram inhibits neutrophil extracellular trap formation protecting rodents from acute lung injury and SARS-CoV-2 infection.

Adrover, Jose M, Carrau, Lucia, Daßler-Plenker, Juliane, Bram, Yaron, Chandar, Vasuretha, Houghton, Sean, Redmond, David, Merrill, Joseph R, Shevik, Margaret, tenOever, Benjamin R, Lyons, Scott K, Schwartz, Robert E, Egeblad, Mikala (February 2022) Disulfiram inhibits neutrophil extracellular trap formation protecting rodents from acute lung injury and SARS-CoV-2 infection. JCI Insight. ISSN 2379-3708

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URL: https://www.ncbi.nlm.nih.gov/pubmed/35133984
DOI: 10.1172/jci.insight.157342

Abstract

Severe acute lung injury has few treatment options and a high mortality rate. Upon injury, neutrophils infiltrate the lungs and form neutrophil extracellular traps (NETs), damaging the lungs and driving an exacerbated immune response. Unfortunately, no drug preventing NET formation has completed clinical development. Here, we report that disulfiram -an FDA-approved drug for alcohol use disorder- dramatically reduced NETs, increased survival, improved blood oxygenation, and reduced lung edema in a transfusion-related acute lung injury (TRALI) mouse model. We then tested whether disulfiram could confer protection in the context of SARS-CoV-2 infection, as NETs are elevated in patients with severe COVID-19. In SARS-CoV-2-infected golden hamsters, disulfiram reduced NETs and perivascular fibrosis in the lungs, and downregulated innate immune and complement/coagulation pathways, suggesting that it could be beneficial for COVID-19 patients. In conclusion, an existing FDA-approved drug can block NET formation and improve disease course in two rodent models of lung injury for which treatment options are limited.

Item Type: Paper
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell cycle > Neutrophil extracellular traps
diseases & disorders > viral diseases > coronavirus > covid 19
organs, tissues, organelles, cell types and functions > organs types and functions > lung
CSHL Authors:
Communities: CSHL labs > Egeblad lab
CSHL labs > Lyons lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 8 February 2022
Date Deposited: 23 Feb 2022 21:43
Last Modified: 11 Apr 2022 13:47
PMCID: PMC8983145
URI: https://repository.cshl.edu/id/eprint/40528

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