Protease-activated receptor 1 as a potential therapeutic target for COVID-19

Author(s)

Rovai, Emanuel S. ^[1] ; Alves, Tomaz ^[2] ; Holzhausen, Marinella ^[2]

Affiliation

^[1] Univ Taubate, Dept Dent, BR-12010490 Taubate, SP - Brazil

^[2] Univ Sao Paulo, Sch Dent, Dept Stomatol, Div Periodont, BR-05508000 Sao Paulo - Brazil

• Document type: Review article
• Source: Experimental Biology and Medicine; v. 246, n. 6, p. 688-694, MAR 2021.
• Web of Science Citations: 1

Abstract

Acute respiratory disease caused by a novel coronavirus (SARS-CoV-2) has spread all over the world, since its discovery in 2019, Wuhan, China. This disease is called COVID-19 and already killed over 1 million people worldwide. The clinical symptoms include fever, dry cough, dyspnea, headache, dizziness, generalized weakness, vomiting, and diarrhea. Unfortunately, so far, there is no validated vaccine, and its management consists mainly of supportive care. Venous thrombosis and pulmonary embolism are highly prevalent in patients suffering from severe COVID-19. In fact, a prothrombotic state seems to be present in most fatal cases of the disease. SARS-CoV-2 leads to the production of proinflammatory cytokines, causing immune-mediated tissue damage, disruption of the endothelial barrier, and uncontrolled thrombogenesis. Thrombin is the key regulator of coagulation and fibrin formation. In severe COVID-19, a dysfunctional of physiological anticoagulant mechanisms leads to a progressive increase of thrombin activity, which is associated with acute respiratory distress syndrome development and a poor prognosis. Protease-activated receptor type 1 (PAR1) is the main thrombin receptor and may represent an essential link between coagulation and inflammation in the pathophysiology of COVID-19. In this review, we discuss the potential role of PAR1 inhibition and regulation in COVID-19 treatment. (AU)

• FAPESP's process: 17/23158-0 - EFFECT OF PROTEASE ACTIVATED RECEPTOR 1 (PAR1) ACTIVATION ON THE OSTEOGENIC ACTIVITY OF MEMBRANES OF HUMAN PERIODONTAL LIGAMENT MESENCHYMAL STEM CELLS
• Grantee: Marinella Holzhausen Caldeira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/13818-5 - Effect of protease-activated receptor type 1 (PAR1) activation on the osteogenic activity in human periodontal ligament stem cells membranes: an in vivo study
• Grantee: Tomaz Alves da Silva Neto
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 19/14846-5 - Evaluation of the salivary proteomic profile in type 2 diabetic patients with periodontitis
• Grantee: Emanuel da Silva Rovai
• Support Opportunities: Regular Research Grants