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SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibito

Hoffman et al., Cell, doi:10.1016/j.cell.2020.02.052
Mar 2020  
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In Vitro study showing that SARS-CoV-2 uses ACE2 for entry and TMPRSS2 for S protein priming, and that TMPRSS2 inhibitor camostat blocked entry and may be an effective treaetment.
Bromhexine efficacy may vary depending on the degree of TMPRSS-dependent fusion for different variants Peacock, Willett.
4 preclinical studies support the efficacy of bromhexine for COVID-19:
Hoffman et al., 5 Mar 2020, peer-reviewed, 13 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
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SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
Markus Hoffmann, Hannah Kleine-Weber, , ..., Simon Schroeder, Nadine Krüger, Tanja Herrler, Sandra Erichsen, Tobias S Schiergens, Georg Herrler, Nai-Huei Wu, Andreas Nitsche, Marcel A Müller, Christian Drosten, Stefan Pöhlmann
Cell, doi:10.1016/j.cell.2020.02.052
Highlights d SARS-CoV-2 uses the SARS-CoV receptor ACE2 for host cell entry d The spike protein of SARS-CoV-2 is primed by TMPRSS2 d Antibodies against SARS-CoV spike may offer some protection against SARS-CoV-2
DECLARATION OF INTERESTS The authors declare no competing interests. 4 (A and B) Importance of endosomal low pH (A) and activity of CatB/L or TMPRSS2 (B) for host cell entry of SARS-CoV-2 was evaluated by adding inhibitors to target cells prior to transduction. Ammonium chloride (A) blocks endosomal acidification while E-64d and camostat mesylate (B) block the activity of CatB/L and TMPRSS2, respectively. Entry into cells not treated with inhibitor was set as 100%. (C) Absence of cytotoxic effects of camostat mesylate. Calu-3 cells were treated with camostat mesylate identically as for infection experiments and cell viability was measured using a commercially available assay (CellTiter-Glo, Promega).
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