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Clomipramine suppresses ACE2-mediated SARS-CoV-2 entry
Yuri Kato; Shigeru Yamada; Kazuhiro Nishiyama; Ayano Satsuka; Suyong Re; Daiki Tomokiyo; Jae Man Lee; Tomohiro Tanaka; Akiyuki Nishimura; Kenzo Yonemitsu; Hiroshi Asakura; Yuko Ibuki; Yumiko Imai; Noriho Kamiya; Kenji Mizuguchi; Takahiro Kusakabe; Yasunari Kanda; Motohiro Nishida.
Afiliación
  • Yuri Kato; Graduate School of Pharmaceutical Sciences, Kyushu University
  • Shigeru Yamada; Division of Pharmacology, National Institute of Health Sciences
  • Kazuhiro Nishiyama; Graduate School of Pharmaceutical Sciences, Kyushu University
  • Ayano Satsuka; Division of Pharmacology, National Institute of Health Sciences
  • Suyong Re; Artificial Intelligence Center for Health and Biomedical Research, National Institutes of Biomedical Innovation, Health and Nutrition
  • Daiki Tomokiyo; Graduate School of Pharmaceutical Sciences, Kyushu University
  • Jae Man Lee; Laboratory of Creative Science for Insect Industries, Faculty of Agriculture, Kyushu University
  • Tomohiro Tanaka; National Institute for Physiological Sciences & Exploratory Research Center on Life and Living Systems, National Institutes of Natural Sciences
  • Akiyuki Nishimura; National Institute for Physiological Sciences & Exploratory Research Center on Life and Living Systems, National Institutes of Natural Sciences
  • Kenzo Yonemitsu; Division of Biomedical Food Research, National Institute of Health Sciences
  • Hiroshi Asakura; Division of Biomedical Food Research, National Institute of Health Sciences
  • Yuko Ibuki; Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka
  • Yumiko Imai; National Institutes of Biomedical Innovation Health and Nutrition
  • Noriho Kamiya; Department of Applied Chemistry, Graduate School of Engineering & Division of Biotechnology, Center for Future Chemistry, Kyushu University
  • Kenji Mizuguchi; National Institutes of Biomedical Innovation, Health and Nutrition & Institute for Protein Research, Osaka University
  • Takahiro Kusakabe; Laboratory of Insect Genome Science, Faculty of Agriculture, Kyushu University
  • Yasunari Kanda; Division of Pharmacology, National Institute of Health Sciences
  • Motohiro Nishida; Graduate School of Pharmaceutical Sciences, Kyushu University & National Institute for Physiological Sciences & Exploratory Research Center on Life and Living S
Preprint en En | PREPRINT-BIORXIV | ID: ppbiorxiv-435221
ABSTRACT
Myocardial damage caused by the newly emerged coronavirus (SARS-CoV-2) infection is one of key determinants of COVID-19 severity and mortality. SARS-CoV-2 entry to host cells are initiated by binding with its receptor, angiotensin converting enzyme (ACE) 2, and the ACE2 abundance is thought to reflect the susceptibility to infection. Here, we found that clomipramine, a tricyclic antidepressant, potently inhibits SARS-CoV-2 infection and metabolic disorder in human iPS-derived cardiomyocytes. Among 13 approved drugs that we have previously identified as potential inhibitor of doxorubicin-induced cardiotoxicity, clomipramine showed the best potency to inhibit SARS-CoV-2 spike glycoprotein pseudovirus-stimulated ACE2 internalization. Indeed, SARS-CoV-2 infection to human iPS-derived cardiomyocytes (iPS-CMs) and TMPRSS2-expressing VeroE6 cells were dramatically suppressed even after treatment with clomipramine. Furthermore, the combined use of clomipramine and remdesivir was revealed to synergistically suppress SARS-CoV-2 infection. Our results will provide the potentiality of clomipramine for the breakthrough treatment of severe COVID-19.
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Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Tipo de estudio: Prognostic_studies Idioma: En Año: 2021 Tipo del documento: Preprint
Texto completo
Añadir a Mi BVS
Imprimir
XML
Buscar en Google
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Tipo de estudio: Prognostic_studies Idioma: En Año: 2021 Tipo del documento: Preprint