OIST - University of Tokyo Mini Talk Series-Nafamostat is an Existing Drug with Multiple Possible Therapeutic Effects on COVID-19
Nafamostat is an existing drug with multiple possible therapeutic effects on COVID-19
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 this key step. Furthermore, nafamostat mesylate blocked SARS-CoV-2 infection of Calu-3 cells with an EC50 of less than 1 nM, which is below its average blood concentration after intravenous administration through continuous infusion. It has been reported recently that abnormal coagulation with elevated concentrations of D-dimer, characteristic of DIC, may influence prognosis for COVID-19 patients. Furthermore, in a murine asthma model, nafamostat mesylate attenuates respiratory inflammation by blocking activation of NF-kB, a critical transcription factor for inflammatory cytokine production. Therefore, nafamostat mesylate is expected to have multiple therapeutic effects. These findings, together with accumulated clinical data regarding nafamostat’s safety, make it a likely candidate drug to treat COVID-19
Senior Prof. Jun-ichiro INOUE, The University of Tokyo
Jun-ichiro Inoue is a senior professor of the University of Tokyo. He received his PhD in Pharmaceutical Sciences at the University of Tokyo. He started to work on human T cell leukemia virus type 1 (HTLV-1), which causes Adult T cell Leukemia (ATL). He then worked on transcription factor NF-kB and its activator TRAF6, especially with regard to the molecular mechanisms of their activation and how they are involved in cancer development. Dr. Inoue is the author of numerous peer-reviewed publications on NF-kB in ATL, breast cancer, autoimmune disease and osteoclastogenesis. Recently, he has been interested in searching for chemical compounds that inhibit infection of envelope viruses such as HIV, flaviviruses and coronaviruses.
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