TMPRSS2-Inhibitors Play a role in Cell Entry Mechanism of COVID-19: An Insight into Camostat and Nafamostat
Journal Title: Journal of Regenerative Biology and Medicine - Year 2020, Vol 2, Issue 2
Abstract
The enzymes trypsin, furin and other proprotein-convertasen, cathepsin, transmembrane proteases (TMPRSS) and elastases play a role by the cell entry of Coronaviren (Coronaviridae)[1]. The proteases TMPRSS2 and TMPRSS11a, which exist in the respiratory tract richly and become experiment on cell surfaces, promote the entry of SARS-CoV-1-virus. For the TMPRSS-protease TMPRSS11d - also as protease similar to trypsin has confessed of the human respiratory tract - a proteolytic activation of the spike protein was proved by SARS-CoV [2]. TMPRSS2 again makes a complex reaction with the ACE2 receptor what allows an efficient penetration of the virus directly in the cell surface [2,3]. TMPRSS2 and TMPRSS11D activate the spike protein, while they split it in the S1 and S2 subunits by which an endosome independence cell entry is allowed in the cell membrane [2,3]. Virus-based therapies enclose monoclonal antibodies, an anti-viral peptide which docks to the spike protein of viruses, inhibitors of the viral nucleic acid synthesis and inhibitors for docking to other viral structures and accessory proteins. Different known serine inhibitors do exist: Gabexate mesylate (Tokyo Chemical Industry, Tokyo, Japan), Nafamostat mesylate (Tokyo Chemical Industry), Camostat mesylate (Wako, Tokyo, Japan), Sivelestat sodium tetrahydrate (LKT Laboratories, St. Paul, MN, USA), rivaroxaban (Adooq Bioscience, Irvine, CA, USA) Telaprevir (Adooq Bioscience) and Simeprevir (TRC, Toronto, Canada) were dissolved in DMSO at a concentration of 10 mm Ulinastatin (Mochida Pharmaceutical Co. Ltd. Tokyo, Japan) was dissolved in PBS (-) which lacked Mg2+ and Ca2+. The FDA approved drug library (L1300) was purchased from Selleck (Houston, TX, USA) and diluted in DMSO at a concentration of 100 μM. Especially in COVID-19, we took a closer look on two main serine protease inhibitors.
Authors and Affiliations
Stefan Bittmann*, Elisabeth Luchter, Anne Weissenstein, Gloria Villalon and Elena Moschüring-Alieva
Keywords
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- EP ID EP707325
- DOI https://doi.org/10.37191/Mapsci-2582-385X-2(2)-022
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