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Lung Protection by Cathepsin C Inhibition: A New Hope for COVID-19 and ARDS?

Authors
  • Korkmaz, Brice1
  • Lesner, Adam2
  • Marchand-Adam, Sylvain1, 3
  • Moss, Celia4
  • Jenne, Dieter E.5
  • 1 INSERM UMR-1100, Centre d’Etude des Pathologies Respiratoires and Université de Tours, France , (France)
  • 2 University of Gdansk, Poland , (Poland)
  • 3 CHRU de Tours, France , (France)
  • 4 Birmingham Children’s Hospital and University of Birmingham, U.K.
  • 5 Munich and Max-Planck Institute of Neurobiology, Germany , (Germany)
Type
Published Article
Journal
Journal of Medicinal Chemistry
Publisher
American Chemical Society
Publication Date
Jul 21, 2020
Identifiers
DOI: 10.1021/acs.jmedchem.0c00776
PMID: 32692176
PMCID: PMC7413214
Source
PubMed Central
License
Green

Abstract

Cathepsin C (CatC) is a cysteine dipeptidyl aminopeptidase that activates most of tissue-degrading elastase-related serine proteases. Thus, CatC appears as a potential therapeutic target to impair protease-driven tissue degradation in chronic inflammatory and autoimmune diseases. A depletion of proinflammatory elastase-related proteases in neutrophils is observed in patients with CatC deficiency (Papillon–Lefèvre syndrome). To address and counterbalance unwanted effects of elastase-related proteases, chemical inhibitors of CatC are being evaluated in preclinical and clinical trials. Neutrophils may contribute to the diffuse alveolar inflammation seen in acute respiratory distress syndrome (ARDS) which is currently a growing challenge for intensive care units due to the outbreak of the COVID-19 pandemic. Elimination of elastase-related neutrophil proteases may reduce the progression of lung injury in these patients. Pharmacological CatC inhibition could be a potential therapeutic strategy to prevent the irreversible pulmonary failure threatening the life of COVID-19 patients.

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