HYPOTHESIS LETTER: Protease-activated receptor 1 (PAR1): A target for
repurposing in the treatment of COVID-19?
Abstract
In the search to rapidly identify effective therapies that will mitigate
the morbidity and mortality of COVID-19, attention has been directed
towards the repurposing of existing drugs. Candidates for repurposing
include drugs that target COVID-19 pathobiology, including agents that
alter angiotensin signaling. Recent data indicate that key findings in
COVID-19 patients include thrombosis and endothelitis Activation of PAR1
(protease activated receptor 1), in particular by the protease thrombin,
is a critical element in platelet aggregation and coagulation. PAR1
activation also impacts on the actions of other cell types involved in
COVID-19 pathobiology, including endothelial cells, fibroblasts and
pulmonary alveolar epithelial cells. Vorapaxar is an approved inhibitor
of PAR1, used for treatment of patients with myocardial infarction or
peripheral arterial disease. Here, we discuss evidence implying a
possible beneficial role for vorapaxar in the treatment of COVID-19
patients and in addition, other as-yet non-approved antagonists of PAR1
and PAR4.