CAMOSTAT DOES NOT INHIBIT THE PROTEOLYTIC ACTIVITY OF NEUTROPHIL SERINE PROTEASES
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Date
2022
Authors
Assylbekova, Akmaral
Zhanapiya, Anuar
Grzywa, Renata
Sienczyk, Marcin
Schönbach, Christian
Journal Title
Journal ISSN
Volume Title
Publisher
Pharmaceuticals
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 ser ine 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 in fection 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.
Description
Keywords
Type of access: Open Access, immunity, chronic inflammatory disorders, cardiovascular diseases
Citation
Assylbekova, A., Zhanapiya, A., Grzywa, R., Sienczyk, M., Schönbach, C., & Burster, T. (2022). Camostat Does Not Inhibit the Proteolytic Activity of Neutrophil Serine Proteases. Pharmaceuticals, 15(5), 500. https://doi.org/10.3390/ph15050500