Bromhexine is a cough suppressant, available over-the-counter in much of the world, that has been proposed as a COVID-19 therapeutic.

Potential mechanism of action

In an NIH study, bromhexine did not directly inhibit the TMPRSS2 enzyme.

Bromhexine has been speculated to inhibit the TMPRSS2 serine protease used by SARS-CoV-2.

In an August 6th, 2020 NIH paper, bromhexine did not directly inhibit TMPRSS2 in vitro.  Study author Matt Hall noted:

"The fact bromhexine is not inhibiting TMPRSS2 doesn't mean it can't work against COVID, and other recent literature in cell models supports our data." -Matt Hall, NIH researcher

In studies of TMPRSS2 in prostate cancer, bromhexine appears to inhibit TMPRSS2 in vivo.  As originally noted by Twitter user ice9, perhaps bromhexine "triggers cells in the lungs to secrete substances that inhibit many serine proteases, likely including TMPRSS2." (reference cited)

A September 14, 2020 preprint showed some evidence that Ambroxol and Bromhexine (a metabolite of Ambroxol), inhibited the SARS-Cov-2 spike protein receptor binding domain ACE2 interaction.

COVID-19 clinical trials

In a small (n=78) open-label, randomized clinical trial of bromhexine was conducted in Iran (July 2020):

"There was a significant reduction in ICU admissions (2 out of 39 vs. 11 out of 39, P=0.006), intubation (1 out of 39 vs. 9 out of 39, P=0.007) and death (0 vs. 5, P=0.027) in the bromhexine treated group compared to the standard group. No patients were withdrawn from the study because of adverse effects."

As of October, 2020, there are two clinical trials of bromhexine registered with currently recruiting participants:

Bromhexine for COVID-19 research reviews

See also