In what could be considered  a striking discovery researchers form Harvard Medical School and Boston Children’s Hospital found that people taking the alcoholism drug disulfiram were 34% less likely to succumb to a SARS-CoV-2 infection, the virus behind COVID-19. Noteworthy none of the participants taking disulfiram died from COVID-19, as compared to 3% of the observational study population not prescribed to the drug used to combat alcoholism.  Could this medicine used to treat alcoholism in the United States for decades be used as a way to lower risk against COVID-19 infection and death? One randomized controlled study sponsored by University of California, San Francisco is ongoing while another one will commence.

In an observational study the research team led by corresponding author Chris Sander, PhD evaluated data from over 944,000 U.S. vets who had at a minimum one COVID-19 test between February 2020 and February 2021. A total of 2,200 of the study subjects were prescribed the alcoholism medication.  The results of the study were recently published in PLOS One and supported the initiation of a small Phase 2 clinical trial of disulfiram in patients with moderate COVID-19. This study is almost complete while another one has purportedly commenced.

What is Disulfiram?

Disulfiram, a safe and inexpensive repurposed drug, is widely used worldwide.  Sold under the trade name Antabuse, the drug triggers an acute sensitivity to ethanol. It works by inhibiting the enzyme acetaldehyde dehydrogenase, triggering many side effects of a hangover felt immediately after alcohol consumption.  The drug has also been studied as a possible treatment for cancer, parasitic infections and latent HIV infection.

Moreover, the drug has been shown to inhibit papain-like proteases of MERS-CoV- and SARS-CoV. It has been studied in the real world and as mentioned is currently undergoing at least one Phase 2 clinical trial. Disulfiram may have both antiviral (inhibiting viral replication via blocking the Mpro protease and zinc ejection) and anti-inflammatory effects (via inhibition of NF-kB-induced and NLRP inflammasome-induced cytokine release) on SARS-CoV-2.Subscribe to the Trialsitenews “COVID-19” ChannelNo spam – we promise

A Randomized Controlled Study

In one disclosed study (NCT04485130) led by Sulggi A. Lee, PhD,  University of California, San Francisco (UCSF) the study team investigates if Disulfiram can be administered safe and easily for the treatment of SARS-CoV-2 infection. The study protocol includes oral disulfiram administered for five consecutive days (1000 mg/day) in 60 symptomatic COVD-19 individual in a randomized (2:1) randomized, double-blind, placebo-controlled trial evaluating the drug’s effect on COVID-19 symptom severity, SARS-CoV-2 viral load, as well as biomarkers of inflammation and pyroptosis (aberrant pro-inflammatory cell death) over a month period.

Involving 60 participants, the study started in May of this year and runs until April 2022.

What took So Long?

TrialSite lamented in article after article during the first year of the pandemic as to the need for drugs that served as antivirals to fight COVID-19.  The NIH and its ACTIV program allocated tens of billions of dollars, focusing on vaccines and novel monoclonal antibodies.  Some of the inherent bias in that programmatic spend can be reviewed here

Finally the government announced a $3 billon research program centering on antivirals but many of the low cost, repurposed drugs TrialSite followed were not necessarily front and center as expensive antivirals from Merck and Pfizer found center stage. 

Now both Merck (molnupiravir) and Pfizer (Paxlovid) seek authorization for the massive COVID-19 market for early treatment. About 90% of all COVID-19 cases represent mild-to-moderate to asymptomatic cases.

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