https://insight.jci.org/articles/view/157342

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

Published February 8, 2022 –

 

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.

Disulfiram has previously been associated in observational studies with lowering the risk of infection from SARS-CoV-2, and one study of the drug in human patients with moderate COVID-19 was completed in 2021, but results haven’t yet been posted. A separate trial testing the drug against COVID-19 in humans has not yet been completed.

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Other drugs approved for different uses have shown some success against COVID-19, including ivermectin, hydroxychloroquine, and fluvoxamine, though U.S. health officials primarily recommend ones such as paxlovid that are specifically approved.

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