Protease inhibitor: Serine proteases. Targets viral cell entry via inhibition of ACE2/TMPRSS2. Hoffmann et al. Cell, 181:1-10, Apr 16 2020, https://doi.org/10.1016/j.cell.2020.02.052; Gordon et al. bioRxiv, Mar 23 2020, https://doi.org/10.1101/2020.03.22.002386; Liu et al. ACS Cent. Sci., 6:315-331, Mar 12 2020, https://doi.org/10.1021/acscentsci.0c00272; Guy et al. Science, 368 829-830 May 22 2020, https://doi.org/10.1126/science.abb9332.
Biochemicals & reagents
1) Gibo et al. (2005), Camostat mesylate attenuates pancreatic fibrosis via inhibition of monocytes and pancreatic stellate cells activity; Lab Invest., 85 75 2) Albarazanji et al. (2019), Intestinal serine protease inhibition increases FGF21 and improves metabolism in obese mice.; Am. J. Physiol. Gastrointest. Liver Physiol., 316 G653 3) Ueda et al. (2015), The serine protease inhibitor camostat mesylate attenuates the progression of chronic kidney disease through its antioxidant effects; Nephron, 129 223 4) Yamaya et al. (2015), The serine protease inhibitor camostat inhibits influenza virus replication and cytokine production in primary cultures of human tracheal epithelial cells; Pulm. Pharmacol. Ther., 33 66 5) Hoffmann et al. (2020), SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor; Cell, Mar. 4 Epub ahead of print
Camostat mesilate is a serine protease inhibitor inhibiting plasmin, kallikrein, thrombin as well as trypsin, which attenuates pancreatic fibrosis (1) and it reduces weight gain and improves metabolism in obese rodent models (2). This compound is in clinical use in Japan for pancreatitis (3). It inhibits influenza virus replication in human tracheal epithelial cells (4) and also reduces infection of Calu-3 lung cells by SARS-CoV-2 (responsible for COVID-19) via inhibition of the serine protease TMPRSS2 required for viral spike protein priming (5).