Bromhexine, an over-the-counter cough suppressant, is commonly used for the treatment of several respiratory disorders, particularly those that involve disturbed mucus secretion. It is a well-tolerated and safe mucolytic agent. 

Bromhexine has been reported to be a selective inhibitor of transmembrane protein serine 2 (TMPRSS2) protease. TMPRSS2 is implicated in the proteolytic activation and invasion of the human airway epithelium by viruses such as influenza, SARS-CoV and MERS.

It is now known that the entry of SARS-CoV-2 in to the cell depends on binding of the viral spike (S) protein to cellular angiotensin converting enzyme 2 receptor and the host cell TMPRSS2 protease primes the S protein.

The interaction between bromhexine and TMPRSS2 enzyme support the evaluation of this drug in patients with COVID-19 infection. Bromhexine had also been proposed earlier as a candidate drug for SARS-CoV and MERS treatment. In pulmonary and bronchial epithelial cells, bromhexine may attain 4 to 6-times higher concentrations compared to those found in the plasma. This concentration is high enough to be able to inhibit TMPRSS2.

Clinical trials of bromhexine, either alone or along with other antivirals agents, should be conducted to determine the potential of this agent in the prevention and treatment of COVID-19 infection.

Reference

Maggio R, Corsini GU. Repurposing the mucolytic cough suppressant and TMPRSS2 protease inhibitor bromhexine for the prevention and management of SARS-CoV-2 infection. Pharmacol Res. 2020 Jul; 157: 104837.