Imatinib (STI571) Inhibits the Expression of Angiotensin-Converting Enzyme 2 and Cell Entry of the SARS-CoV-2-Derived Pseudotyped Viral Particles
A group of clinically approved cancer therapeutic tyrosine kinase inhibitors was screened to test their effects on the expression of angiotensin-converting enzyme 2 (ACE2), the cell surface receptor for SARS-CoV-2. Here, we show that the receptor tyrosine kinase inhibitor imatinib (also known as STI...
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| Format: | Article |
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/13/6938 |
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| author | You-Zhe Lin Yi-Chun Shen Wan-Rong Wu Wei-Jan Wang Yuan-Liang Wang Chen-Yuan Lin Mien-Chie Hung Shao-Chun Wang |
| author_facet | You-Zhe Lin Yi-Chun Shen Wan-Rong Wu Wei-Jan Wang Yuan-Liang Wang Chen-Yuan Lin Mien-Chie Hung Shao-Chun Wang |
| author_sort | You-Zhe Lin |
| collection | DOAJ |
| description | A group of clinically approved cancer therapeutic tyrosine kinase inhibitors was screened to test their effects on the expression of angiotensin-converting enzyme 2 (ACE2), the cell surface receptor for SARS-CoV-2. Here, we show that the receptor tyrosine kinase inhibitor imatinib (also known as STI571, Gleevec) can inhibit the expression of the endogenous ACE2 gene at both the transcript and protein levels. Treatment with imatinib resulted in inhibition of cell entry of the viral pseudoparticles (Vpps) in cell culture. In FVB mice orally fed imatinib, tissue expression of ACE2 was reduced, specifically in the lungs and renal tubules, but not in the parenchyma of other organs such as the heart and intestine. Our finding suggests that receptor tyrosine kinases play a role in COVID-19 infection and can be therapeutic targets with combined treatments of the best conventional care of COVID-19. |
| first_indexed | 2024-03-09T04:48:08Z |
| format | Article |
| id | doaj.art-9b31b813a97f45329116d1eece8c7405 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T04:48:08Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9b31b813a97f45329116d1eece8c74052023-12-03T13:13:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012213693810.3390/ijms22136938Imatinib (STI571) Inhibits the Expression of Angiotensin-Converting Enzyme 2 and Cell Entry of the SARS-CoV-2-Derived Pseudotyped Viral ParticlesYou-Zhe Lin0Yi-Chun Shen1Wan-Rong Wu2Wei-Jan Wang3Yuan-Liang Wang4Chen-Yuan Lin5Mien-Chie Hung6Shao-Chun Wang7Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung 40402, TaiwanGraduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung 40402, TaiwanGraduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung 40402, TaiwanResearch Center for Cancer Biology, China Medical University, Taichung 40402, TaiwanGraduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung 40402, TaiwanDepartment of Hematology and Oncology, China Medical University Hospital, Taichung 404332, TaiwanGraduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung 40402, TaiwanGraduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung 40402, TaiwanA group of clinically approved cancer therapeutic tyrosine kinase inhibitors was screened to test their effects on the expression of angiotensin-converting enzyme 2 (ACE2), the cell surface receptor for SARS-CoV-2. Here, we show that the receptor tyrosine kinase inhibitor imatinib (also known as STI571, Gleevec) can inhibit the expression of the endogenous ACE2 gene at both the transcript and protein levels. Treatment with imatinib resulted in inhibition of cell entry of the viral pseudoparticles (Vpps) in cell culture. In FVB mice orally fed imatinib, tissue expression of ACE2 was reduced, specifically in the lungs and renal tubules, but not in the parenchyma of other organs such as the heart and intestine. Our finding suggests that receptor tyrosine kinases play a role in COVID-19 infection and can be therapeutic targets with combined treatments of the best conventional care of COVID-19.https://www.mdpi.com/1422-0067/22/13/6938COVID-19ACE2imatinibtyrosine kinase |
| spellingShingle | You-Zhe Lin Yi-Chun Shen Wan-Rong Wu Wei-Jan Wang Yuan-Liang Wang Chen-Yuan Lin Mien-Chie Hung Shao-Chun Wang Imatinib (STI571) Inhibits the Expression of Angiotensin-Converting Enzyme 2 and Cell Entry of the SARS-CoV-2-Derived Pseudotyped Viral Particles International Journal of Molecular Sciences COVID-19 ACE2 imatinib tyrosine kinase |
| title | Imatinib (STI571) Inhibits the Expression of Angiotensin-Converting Enzyme 2 and Cell Entry of the SARS-CoV-2-Derived Pseudotyped Viral Particles |
| title_full | Imatinib (STI571) Inhibits the Expression of Angiotensin-Converting Enzyme 2 and Cell Entry of the SARS-CoV-2-Derived Pseudotyped Viral Particles |
| title_fullStr | Imatinib (STI571) Inhibits the Expression of Angiotensin-Converting Enzyme 2 and Cell Entry of the SARS-CoV-2-Derived Pseudotyped Viral Particles |
| title_full_unstemmed | Imatinib (STI571) Inhibits the Expression of Angiotensin-Converting Enzyme 2 and Cell Entry of the SARS-CoV-2-Derived Pseudotyped Viral Particles |
| title_short | Imatinib (STI571) Inhibits the Expression of Angiotensin-Converting Enzyme 2 and Cell Entry of the SARS-CoV-2-Derived Pseudotyped Viral Particles |
| title_sort | imatinib sti571 inhibits the expression of angiotensin converting enzyme 2 and cell entry of the sars cov 2 derived pseudotyped viral particles |
| topic | COVID-19 ACE2 imatinib tyrosine kinase |
| url | https://www.mdpi.com/1422-0067/22/13/6938 |
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