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Author Spotlight: Developing Parmodulins to Target Protease-Activated Receptors for Inflammation Control
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Proteinase-activated receptor 1: A target for repurposing in the treatment of COVID-19?

Krishna Sriram1, Paul A Insel1,2

  • 1Department of Pharmacology, University of California San Diego, La Jolla, CA, USA.

British Journal of Pharmacology
|July 9, 2020
PubMed

Insights

Drug repurposing for COVID-19 may involve targeting thrombosis and endotheliitis. Vorapaxar, a proteinase-activated receptor 1 (PAR1) inhibitor, shows potential therapeutic benefits for COVID-19 patients by modulating coagulation pathways.

Area of Science:

  • Pharmacology
  • Infectious Diseases
  • Cardiovascular Research

Background:

  • COVID-19 presents significant morbidity and mortality, necessitating rapid therapeutic identification.
  • Drug repurposing is a key strategy, with a focus on agents targeting COVID-19 pathobiology, including angiotensin signaling.
  • Key pathological findings in COVID-19 include thrombosis and endotheliitis, suggesting a role for anticoagulation therapies.

Purpose of the Study:

  • To explore the potential therapeutic role of vorapaxar, a proteinase-activated receptor 1 (PAR1) antagonist, in managing COVID-19.
  • To discuss the evidence supporting the use of PAR1 and PAR4 antagonists for treating COVID-19 complications.

Main Methods:

  • Review of existing literature on COVID-19 pathobiology, thrombosis, and endotheliitis.
  • Analysis of the mechanism of action of vorapaxar as a PAR1 inhibitor.
  • Discussion of the potential impact of PAR1 and PAR4 antagonism on COVID-19-related cellular processes.

Main Results:

  • Activation of proteinase-activated receptor 1 (PAR1) by thrombin is crucial for platelet aggregation and coagulation.
  • PAR1 activation influences endothelial cells, fibroblasts, and pulmonary alveolar epithelial cells, all implicated in COVID-19.
  • Vorapaxar, an approved PAR1 inhibitor, is investigated for its potential to mitigate COVID-19-related thrombosis and endotheliitis.

Conclusions:

  • Vorapaxar and other PAR1/PAR4 antagonists represent a promising avenue for drug repurposing in COVID-19 treatment.
  • Targeting PAR1 may offer a beneficial therapeutic strategy to address the thrombotic and inflammatory aspects of severe COVID-19.

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