Eco-pharma research focusing on ACE2-mediated SARS-CoV-2 entry

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  • Yuri Kato
    Department of Physiology, Graduate School of Pharmaceutical Sciences, Kyushu University
  • Kanda Yasunari
    Division of Pharmacology, National Institute of Health Sciences (NIHS)
  • Nishida Motohiro
    Department of Physiology, Graduate School of Pharmaceutical Sciences, Kyushu University Division of Cardiocirculatory Signaling, National Institutes of Natural Sciences

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Other Title
  • SARS-CoV-2のACE2を介する細胞内侵入に着目したエコファーマ研究

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<p>Myocardial damage caused by the newly emerged coronavirus (SARS-CoV-2) infection is one of key determinants of COVID-19 severity and mortality. Effective treatments for COVID-19 have not yet been established. The main pathway of infection is that the Spike protein on the surface of SARS-CoV-2 binds to its recognition receptor, angiotensin converting enzyme (ACE) 2, on the host cell. 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 protein 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. These results provide the potentiality of clomipramine for improving COVID-19 aggravation and sequelae.</p>

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