Hot Topics: Endothelin-1 pathway, a new therapeutic target for COVID-19

SARS-CoV-2 gains entry into the body mainly via the lungs. After entering the blood, the virus rapidly multiplies to infect nearby cells. Endothelial cells line every blood vessel and have a surface area similar to a tennis court. These cells are especially vulnerable to virus infection as they express the the virus entry receptor, ACE2. Endothelial cells are also a source of endothelin-1 (ET-1), which is released in response to injury to cause long lasting vasoconstriction, reducing oxygen supply to vital organs. In the lungs, this can cause breathing difficulty, which in severe cases requires patients to be given oxygen and put on a ventilator.

The study compared ET-1 in the plasma of patients infected with COVID-19 who were hospitalised during the first wave of the pandemic, including those placed on ventilators (1). Significantly higher levels of ET-1 were measured in these patients, compared with infected individuals with mild or no symptoms. The release of multiple copies of the virus following infection is known to damage endothelial cells and the results show stored ET-1 is also released into the bloodstream.

Currently, medicines that block the detrimental actions of ET-1 are used to treat rare forms of lung disease that share some of the clinical features of COVID-19 infection. The results provide evidence to support testing these medicines in clinical trials to see if they would benefit the most severely affected patients. The virus continues to evolve and in addition to vaccines and bespoke antivirals, that may be susceptible to the development of resistance, it is important to develop alternative ways to block the harmful actions of the virus. By targeting the damaging actions of SARS-CoV-2 on the host cells, medicines are likely to remain effective irrespective of evolving mutations in the virus.

  1. Abraham GR, Kuc RE, Althage M, Greasley PJ, Ambery P, Maguire JJ, Wilkinson IB, Hoole SP, Cheriyan J, Davenport AP. Endothelin-1 is increased in the plasma of patients hospitalised with Covid-19. J Mol Cell Cardiol. 2022 Mar 23:S0022-2828(22)00051-7. doi: 10.1016/j.yjmcc.2022.03.007. PMID: 35339512.

Comments by the Guide to Pharmacology Curation Team, University of Edinburgh

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