Camostat Does Not Inhibit the Proteolytic Activity of Neutrophil Serine Proteases

Akmaral Assylbekova, Anuar Zhanapiya, Renata Grzywa, Marcin Sienczyk, Christian Schönbach, Timo Burster

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Coronavirus disease 2019 (COVID-19) can lead to multi-organ failure influenced by co-morbidities and age. Binding of the severe acute respiratory syndrome coronavirus 2 spike protein (SARS-CoV-2 S protein) to angiotensin-converting enzyme 2 (ACE2), along with proteolytic digestion of the S protein by furin and transmembrane protease serine subtype 2 (TMPRSS2), provokes inter-nalization of SARS-CoV-2 into the host cell. Productive infection occurs through viral replication in the cytosol and cell-to-cell transmission. The catalytic activity of TMPRSS2 can be blocked by the trypsin-like serine protease inhibitor camostat, which impairs infection by SARS-CoV-2. At the site of infection, immune cells, such as neutrophils, infiltrate and become activated, releasing neutrophil serine proteases (NSPs), including cathepsin G (CatG), neutrophil elastase (NE), and proteinase 3 (PR3), which promote the mounting of a robust immune response. However, NSPs might be involved in infection and the severe outcome of COVID-19 since the uncontrolled proteolytic activity is responsible for many complications, including autoimmunity, chronic inflammatory disorders, cardiovascular diseases, and thrombosis. Here, we demonstrate that camostat does not inhibit the catalytic activity of CatG, NE, and PR3, indicating the need for additional selective serine protease inhibitors to reduce the risk of developing severe COVID-19.

Original languageEnglish
Article number500
JournalPharmaceuticals
Volume15
Issue number5
DOIs
Publication statusPublished - May 2022

Keywords

  • camostat
  • cathepsin G
  • COVID-19
  • neutrophil elastase
  • proteinase 3
  • SARS-CoV-2
  • serine proteases

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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