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Comment
. 2020 May 21;64(6):e00754-20.
doi: 10.1128/AAC.00754-20. Print 2020 May 21.

Nafamostat Mesylate Blocks Activation of SARS-CoV-2: New Treatment Option for COVID-19

Markus Hoffmann  1   2 , Simon Schroeder  3   4 , Hannah Kleine-Weber  1   2 , Marcel A Müller  3   4   5 , Christian Drosten  3   4 , Stefan Pöhlmann  6   2
Affiliations
Comment

Nafamostat Mesylate Blocks Activation of SARS-CoV-2: New Treatment Option for COVID-19

Markus Hoffmann et al. Antimicrob Agents Chemother. .
No abstract available

Keywords: COVID-19; SARS-CoV-2; TMPRSS2; coronavirus.

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Figures

FIG 1
FIG 1
Nafamostat mesylate inhibits SARS-CoV-2 infection of lung cells in the nanomolar range. The lung-derived human cell line Calu-3 was incubated with the indicated concentrations of the indicated serine protease inhibitors, and (A) either cell viability was measured or the cells were inoculated with vesicular stomatitis virus reporter particles pseudotyped with the indicated viral glycoproteins. The efficiency of viral entry was determined at 16 h postinoculation by measuring luciferase activity in cell lysates. The 50% effective dose values are indicated below the graphs. In parallel, cells exposed to serine protease inhibitors were infected with replication-competent vesicular stomatitis virus encoding green fluorescent protein (B) or infected with SARS-CoV-2 (C), and infection efficiency was quantified by focus formation assay and by measuring genome copies via quantitative RT-PCR, respectively. A scheme of how camostat and nafamostat mesylate block activation of SARS-2-S is shown in panel D. The average from three independent experiments is shown in panels A and C while the average from four independent experiments is presented in panel B. For panels A to C, statistical significance was tested by two-way analysis of variance with Dunnett’s posttest. In addition, statistical significance of differences between SARS-CoV-2 genome equivalents at identical concentrations of camostat or nafamostat mesylate was tested by one-way analysis of variance with Sidak’s posttest. Abbreviations: VSV-G, vesicular stomatitis virus glycoprotein, MACV-GPC, Machupo virus glycoprotein complex; MERS-S, Middle East respiratory syndrome coronavirus spike glycoprotein; SARS-S, severe acute respiratory syndrome coronavirus spike glycoprotein; SARS-2-S, severe acute respiratory syndrome coronavirus 2 spike glycoprotein.
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