Serine proteases are the largest class of mammalian proteases. Serine proteases exist in all kingdoms of cellular life as well as many viral genomes. Over one-third of all known proteolytic enzymes are serine proteases grouped into 13 clans and 40 families, including neutrophil elastase, cathespin G, proteinase 3, plasminogen activators, ganymede, and type II transmembrane serine proteases. The family name stems from the nucleophilic Ser in the enzyme active site, which attacks the carbonyl moiety of the substrate peptide bond to form an acyl-enzyme intermediate. Serine proteases are usually endoproteases and optimally active at neutral pH and play major roles in extracellular proteolysis.

Serine proteases cleave various extracellular proteins to contribute to tissue remodeling, inflammation, and host defense against bacteria. However, when their activity is excessive, serine proteases also contribute to the pathogenesis of the chronic obstructive pulmonary disease, cystic fibrosis, acute lung injury, pulmonary fibrosis, and respiratory viral infections. Serine proteases also cleave proteins expressed by influenza viruses and coronaviruses to promote viral entry into cells and viral pathogenicity.

Camostat is an orally active serine protease inhibitor.

Camostat is an orally active inhibitor of serine protease for chronic pancreatitis. Specifically, Camostat can inhibit trypsin as well as various inflammatory proteases, including plasmin, kallikrein and thrombin. Camostat also is a reversible airway epithelial sodium channel (ENaC) attenuator. Camostat inhibits both monocyte chemoattractant protein-1 (MCP-1) and TNF-α production from monocytes. Meanwhile, it also inhibits the activity of pancreatic stellate cells. Camostat regulates the cytokine expression and inflammation and suppresses pancreatitis-induced pain in rats following oral administration. What’s more, Camostat also inhibits SARS-CoV-2 infection of lung cells by blocking the virus-activating host cell protease TMPRSS2.

In summary, Camostat is an orally active, synthetic serine protease inhibitor for chronic pancreatitis. Camostat also shows antiviral activity against SARS-CoV-2 by inhibits TMPRSS2.

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