Thrombin activates proteinase activated receptors (PARs) that signal through heterotrimeric G proteins of the G12/13 and Gq families. In human platelets, PAR1 (F2R) is the predominant thrombin receptor. Gq is necessary for platelet secretion and aggregation in response to thrombin but is not necessary for thrombin-triggered shape change. G13 appears to contribute to platelet aggregation as well as shape change in response to low concentrations of thrombin but to be unnecessary at higher agonist concentrations; G12 appears to be dispensable for thrombin signaling in platelets.

Vorapaxar is a tricyclic himbacine-derived selective inhibitor of F2R which leads to the prevention of thrombin-related platelet aggregation (Bonaca & Morrow 2009, Ueno et al. 2010). Vorapaxar is indicated for reducing the incidence of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease.

From recent data, key findings in COVID-19 patients include thrombosis and endotheliitis. Activation of F2R, in particular by thrombin, is a critical element in platelet aggregation and coagulation. F2R activation also impacts on the actions of other cell types involved in COVID-19 pathobiology, including endothelial cells, fibroblasts and pulmonary alveolar epithelial cells. Antagonism of F2R by vorapaxar may have a possible beneficial role in the treatment of COVID-19 patients (Sriram & Insel 2020).