Related Experiment Video
Updated: Oct 2, 2025
08:41
Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
Published on: November 5, 2021
2.9K
[Eco-pharma research aimed at developing COVID-19 therapeutic agent]
Yuri Kato1, Kazuhiro Nishiyama1, Akiyuki Nishimura2
1Graduate School of Pharmaceutical Science, Kyushu University.
Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
|March 1, 2022
Summary
COVID-19 infection can cause heart failure by upregulating cardiac angiotensin converting enzyme 2 (ACE2) receptors. A study identified clomipramine as a potential drug to block this ACE2 upregulation, offering a new therapeutic strategy for severe COVID-19.
Area of Science:
- Cardiology
- Virology
- Pharmacology
Background:
- COVID-19, caused by SARS-CoV-2, is a global pandemic with no established therapy.
- The virus enters host cells via the Spike protein binding to angiotensin converting enzyme 2 (ACE2) receptors.
- ACE2 is present in various organs, including the heart, and its dysregulation is linked to COVID-19 complications like heart failure.
Purpose of the Study:
- To investigate the molecular mechanism of pathological ACE2 upregulation in the heart during COVID-19.
- To identify potential therapeutic strategies to prevent COVID-19-related heart failure.
Main Methods:
- Examined the role of TRPC3 and NADPH oxidase (Nox) 2 in myocardial remodeling and ACE2 upregulation.
- Utilized an in vitro pseudo-infection screening system to test approved drugs for their ability to inhibit ACE2 internalization.
Main Results:
- Cardiac ACE2 receptors are upregulated by environmental stresses associated with COVID-19 aggravation.
- Formation of a TRPC3-Nox2 protein complex contributes to pathological ACE2 upregulation in the heart.
- Clomipramine, a tricyclic antidepressant, demonstrated potent inhibition of SARS-CoV-2 Spike protein-induced ACE2 internalization.
Conclusions:
- The TRPC3-Nox2 complex mediates pathological ACE2 upregulation in cardiac tissue, contributing to heart failure risk in COVID-19.
- Clomipramine emerges as a promising drug candidate for therapeutic intervention against COVID-19-related cardiac complications.
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