Disulfiram (Antabuse) A Cheap 70 Year Old Alcoholism Drug May Protect the Lungs from COVID-19 Damage

Disulfiram sold under the name of Antabuse is prescribed to treat alcoholism, but researchers at Weil Medical College have also found that it reduces coronavirus damage in hamster lungs.

Disulfiram Tablets

Disulfiram Tablets

Disulfiram Repurposed

The therapeutic effect of disulfiram has been known for almost 70 years. It was originally used as an antiparasitic but is now prescribed for alcohol dependence. Disulfiram inhibits the action of an enzyme involved in the elimination of alcohol in the body. The molecule, therefore, intensifies the symptoms of a “hangover,” which is a means of discouraging alcoholics from consuming alcohol again.

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A drug approved for one disease is often retested to evaluate its effect on another disease to see if it could be repurposed for another condition. This is what happened with disulfiram. In 2020, researchers observed that the molecule limits the formation of NETs (neutrophil extracellular traps), an extracellular structure that neutrophil white blood cells deploy like a spider web to trap pathogens. These NETs are present in the lungs of some Covid-19 patients and can attack lung tissues and vessels.

“The NETs can damage tissue, but because disulfiram affects the Gasdermin D, a molecule needed to produce NETs; no NETs are formed after disulfiram treatment,” explains Mikala Egelbad, first author of the study published in the JCI insight.

Positive preclinical trials

After in vitro tests showed that disulfiram prevents neutrophils from unfolding their networks, the researchers conducted preclinical tests in golden hamsters with Covid-19. Taking disulfiram one day before and one day after infection with SARS-CoV-2 reduces NETs formation and thus tissue damage in the lungs (fibrosis) and also eliminates harmful inflammation.

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The researchers tested disulfiram in mice with transfusion-related acute lung injury (TRALI), which is acute respiratory distress following blood transfusion. Treatment with disulfiram significantly increased the survival of the group of treated mice compared to the untreated ones. A small clinical trial involving 60 Covid-19 patients is underway at the University of California San Francisco to confirm the positive effects of disulfiram.

References

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

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