About: The Anticoagulant Nafamostat Potently Inhibits SARS-CoV-2 S Protein-Mediated Fusion in a Cell Fusion Assay System and Viral Infection In Vitro in a Cell-Type-Dependent Manner

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About: The Anticoagulant Nafamostat Potently Inhibits SARS-CoV-2 S Protein-Mediated Fusion in a Cell Fusion Assay System and Viral Infection In Vitro in a Cell-Type-Dependent Manner Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	The Anticoagulant Nafamostat Potently Inhibits SARS-CoV-2 S Protein-Mediated Fusion in a Cell Fusion Assay System and Viral Infection In Vitro in a Cell-Type-Dependent Manner
Creator	Takeda, Makoto Kawaoka, Yoshihiro Ohmagari, Norio Imai, Masaki Inoue, Jun-Ichiro Yamamoto, Mizuki Iwatsuki-Horimoto, Kiyoko Kiso, Maki Kawaguchi, Yasushi Matsuda, Zene Sakai-Tagawa, Yuko Kinoshita, Noriko Gohda, Jin Semba, Kentaro
Source	Medline; PMC
abstract	Although infection by SARS-CoV-2, the causative agent of coronavirus pneumonia disease (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 Middle East respiratory syndrome coronavirus (MERS-CoV) S protein-mediated cell fusion by targeting transmembrane serine protease 2 (TMPRSS2), and inhibited MERS-CoV infection of human lung epithelium-derived Calu-3 cells. Here we established a quantitative fusion assay dependent on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein, angiotensin I converting enzyme 2 (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 effective concentration (EC)(50) around 10 nM, which is below its average blood concentration after intravenous administration through continuous infusion. On the other hand, a significantly higher dose (EC(50) around 30 μM) was required for VeroE6/TMPRSS2 cells, where the TMPRSS2-independent but cathepsin-dependent endosomal infection pathway likely predominates. Together, our study shows that nafamostat mesylate potently inhibits SARS-CoV-2 S protein-mediated fusion in a cell fusion assay system and also inhibits SARS-CoV-2 infection in vitro in a cell-type-dependent manner. These findings, together with accumulated clinical data regarding nafamostat’s safety, make it a likely candidate drug to treat COVID-19.
has issue date	2020-06-10(xsd:dateTime)
bibo:doi	10.3390/v12060629
bibo:pmid	32532094
has license	cc-by
sha1sum (hex)	8e40ecbb0139452d8183261338ab69db1ee0c662
schema:url	https://doi.org/10.3390/v12060629
resource representing a document's title	The Anticoagulant Nafamostat Potently Inhibits SARS-CoV-2 S Protein-Mediated Fusion in a Cell Fusion Assay System and Viral Infection In Vitro in a Cell-Type-Dependent Manner
has PubMed Central identifier	PMC7354595
has PubMed identifier	32532094
schema:publication	Viruses
resource representing a document's body	covid:8e40ecbb0139452d8183261338ab69db1ee0c662#body_text
is schema:about of	named entity 'disseminated intravascular coagulation' named entity 'MERS-CoV' named entity 'coronavirus' named entity 'mesylate' named entity 'Fusion' named entity 'TRANSMEMBRANE' named entity 'LUNG EPITHELIUM' named entity 'SARS-COV-2' named entity 'CORONAVIRUS' named entity 'CALU-3' covid:arg/8e40ecbb0139452d8183261338ab69db1ee0c662 named entity 'MERS-CoV' named entity 'treating' named entity 'drug' named entity 'infection' named entity 'Japan' named entity 'nafamostat' named entity 'protease inhibitor' named entity 'enzyme' named entity 'transmembrane serine protease 2' named entity 'Thermo Scientific' named entity 'infection' named entity 'mesylate' named entity 'puromycin' named entity 'TMPRSS2' named entity 'SARS-CoV-2' named entity 'NF-κB' named entity 'epithelial cells' named entity 'enzyme' named entity 'infection' named entity 'nafamostat' named entity 'lung' named entity 'co-culture' named entity 'mesylate' named entity 'protein' named entity 'SARS-CoV-2' named entity 'culture medium' named entity 'epithelial cells' named entity 'cell fusion' named entity 'SARS-CoV-2' named entity 'viral envelope' named entity 'angiotensin converting enzyme 2' named entity 'protein' named entity 'transfecting' named entity 'Multidrop' named entity 'geneticin' named entity 'mesylate' named entity 'infection' named entity 'SARS-CoV-2' named entity 'co-culture' named entity 'cloned' named entity 'University of Tokyo' named entity 'ACE2' named entity 'plasma membrane' named entity 'rivaroxaban' named entity 'lung' named entity 'SARS-CoV-2' named entity 'nafamostat' named entity 'TMPRSS2' named entity 'cell fusion' named entity 'fetal' named entity 'epithelial cell' named entity 'SARS-CoV-2' named entity 'viruses' named entity 'effector' named entity 'substrate' named entity 'lentiviral' named entity 'protein'

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