RT Journal Article SR Electronic T1 The anticoagulant nafamostat potently inhibits SARS-CoV-2 infection in vitro: an existing drug with multiple possible therapeutic effects JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.04.22.054981 DO 10.1101/2020.04.22.054981 A1 Mizuki Yamamoto A1 Maki Kiso A1 Yuko Sakai-Tagawa A1 Kiyoko Iwatsuki-Horimoto A1 Masaki Imai A1 Makoto Takeda A1 Noriko Kinoshita A1 Norio Ohmagari A1 Jin Gohda A1 Kentaro Semba A1 Zene Matsuda A1 Yasushi Kawaguchi A1 Yoshihiro Kawaoka A1 Jun-ichiro Inoue YR 2020 UL http://biorxiv.org/content/early/2020/04/23/2020.04.22.054981.abstract AB Although infection by SARS-CoV-2, the causative agent of COVID-19, is spreading rapidly worldwide, no drug has been shown to be sufficiently effective for treating COVID-19. We previously found that nafamostat mesylate, an existing drug used for disseminated intravascular coagulation (DIC), effectively blocked MERS-CoV S protein-initiated cell fusion by targeting TMPRSS2, and inhibited MERS-CoV infection of human lung epithelium-derived Calu-3 cells. Here we established a quantitative fusion assay dependent on SARS-CoV-2 S protein, ACE2 and TMPRSS2, and found that nafamostat mesylate potently inhibited the fusion while camostat mesylate was about 10-fold less active. Furthermore, nafamostat mesylate blocked SARS-CoV-2 infection of Calu-3 cells with an EC50 around 10 nM, which is below its average blood concentration after intravenous administration through continuous infusion. These findings, together with accumulated clinical data regarding its safety, make nafamostat a likely candidate drug to treat COVID-19.Competing Interest StatementThe authors have declared no competing interest.