Proteinase-activated receptor 1: 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 signalling. Recent data indicate that key findings in COVID-19 patients include thrombosis and endotheliitis. Activation of proteinase-activated receptor 1 (PAR1), in particular by the serine 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. We discuss evidence for a possible beneficial role for vorapaxar in the treatment of COVID-19 patients and other as-yet non-approved antagonists of PAR1 and proteinase-activated receptor 4 (PAR4). LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.

• Authors: Krishna Sriram, Paul A Insel
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 177 Issue 21 Pg. 4971-4974 (11 2020) ISSN: 1476-5381 [Electronic] England
• PMID: 32639031 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The British Pharmacological Society.

Chemical References

• Lactones
• Platelet Aggregation Inhibitors
• Pyridines
• Receptor, PAR-1
• Receptors, Thrombin
• protease-activated receptor 4
• vorapaxar

Topics

• Animals
• Betacoronavirus (isolation & purification)
• COVID-19
• Coronavirus Infections (drug therapy, virology)
• Drug Repositioning
• Humans
• Lactones (administration & dosage, pharmacology)
• Pandemics
• Platelet Aggregation Inhibitors (administration & dosage, pharmacology)
• Pneumonia, Viral (drug therapy, virology)
• Pyridines (administration & dosage, pharmacology)
• Receptor, PAR-1 (antagonists & inhibitors, metabolism)
• Receptors, Thrombin (antagonists & inhibitors, metabolism)
• SARS-CoV-2
• COVID-19 Drug Treatment