Daphnetin may protect from SARS-CoV-2 infection by reducing ACE2
Abstract To combat the SARS-CoV-2 pandemic, innovative prevention strategies are needed, including reducing ACE2 expression on respiratory cells. This study screened approved drugs in China for their ability to downregulate ACE2. Daphnetin (DAP) was found to significantly reduce ACE2 mRNA and protei...
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| Format: | Article |
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Nature Portfolio
2024-12-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-79734-z |
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| author | Qian-wen Yang Chang-ling Yue Meng Chen Yun-yun Ling Qi Dong Ying-xin Zhou Yin Cao Yan-xia Ding Xu Zhao Hai Huang Zhao-huan Zhang Lei Hu Xiao-hui Xu |
| author_facet | Qian-wen Yang Chang-ling Yue Meng Chen Yun-yun Ling Qi Dong Ying-xin Zhou Yin Cao Yan-xia Ding Xu Zhao Hai Huang Zhao-huan Zhang Lei Hu Xiao-hui Xu |
| author_sort | Qian-wen Yang |
| collection | DOAJ |
| description | Abstract To combat the SARS-CoV-2 pandemic, innovative prevention strategies are needed, including reducing ACE2 expression on respiratory cells. This study screened approved drugs in China for their ability to downregulate ACE2. Daphnetin (DAP) was found to significantly reduce ACE2 mRNA and protein levels in PC9 cells. DAP exerts its inhibitory effects on ACE2 expression by targeting HIF-1α and JAK2, thereby impeding the transcription of the ACE2 gene. The SARS-CoV-2 pseudovirus infection assay confirmed that DAP-treated PC9 cells exhibited decreased susceptibility to viral infection. At therapeutic doses, DAP effectively lowers ACE2 expression in the respiratory systems of mice and humans. This suggests that DAP, already approved for other conditions, could be a new preventive measure against SARS-CoV-2, offering a cost-effective and accessible way to reduce SARS-CoV-2 spread. |
| format | Article |
| id | doaj-art-c7187b2a0b654c8693e1a67f865032d9 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-c7187b2a0b654c8693e1a67f865032d92025-08-20T02:57:33ZengNature PortfolioScientific Reports2045-23222024-12-0114111210.1038/s41598-024-79734-zDaphnetin may protect from SARS-CoV-2 infection by reducing ACE2Qian-wen Yang0Chang-ling Yue1Meng Chen2Yun-yun Ling3Qi Dong4Ying-xin Zhou5Yin Cao6Yan-xia Ding7Xu Zhao8Hai Huang9Zhao-huan Zhang10Lei Hu11Xiao-hui Xu12School of Life Sciences, Shanghai UniversitySchool of Life Sciences, Shanghai UniversitySchool of Preclinical Medicine, Wannan Medical CollegeDepartment of Chemistry, Wannan Medical CollegeSchool of Preclinical Medicine, Wannan Medical CollegeSchool of Preclinical Medicine, Wannan Medical CollegeSchool of Preclinical Medicine, Wannan Medical CollegeSchool of Preclinical Medicine, Wannan Medical CollegeSchool of Preclinical Medicine, Wannan Medical CollegeSchool of Life Sciences, Shanghai UniversityDepartment of Laboratory Medicine, Changzheng Hospital, Naval Medical UniversitySchool of Preclinical Medicine, Wannan Medical CollegeSchool of Preclinical Medicine, Wannan Medical CollegeAbstract To combat the SARS-CoV-2 pandemic, innovative prevention strategies are needed, including reducing ACE2 expression on respiratory cells. This study screened approved drugs in China for their ability to downregulate ACE2. Daphnetin (DAP) was found to significantly reduce ACE2 mRNA and protein levels in PC9 cells. DAP exerts its inhibitory effects on ACE2 expression by targeting HIF-1α and JAK2, thereby impeding the transcription of the ACE2 gene. The SARS-CoV-2 pseudovirus infection assay confirmed that DAP-treated PC9 cells exhibited decreased susceptibility to viral infection. At therapeutic doses, DAP effectively lowers ACE2 expression in the respiratory systems of mice and humans. This suggests that DAP, already approved for other conditions, could be a new preventive measure against SARS-CoV-2, offering a cost-effective and accessible way to reduce SARS-CoV-2 spread.https://doi.org/10.1038/s41598-024-79734-zSevere acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2)Angiotensin-converting enzyme 2 (ACE2)Daphnetin (DAP)PreventionHIF-1αJAK2 |
| spellingShingle | Qian-wen Yang Chang-ling Yue Meng Chen Yun-yun Ling Qi Dong Ying-xin Zhou Yin Cao Yan-xia Ding Xu Zhao Hai Huang Zhao-huan Zhang Lei Hu Xiao-hui Xu Daphnetin may protect from SARS-CoV-2 infection by reducing ACE2 Scientific Reports Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) Angiotensin-converting enzyme 2 (ACE2) Daphnetin (DAP) Prevention HIF-1α JAK2 |
| title | Daphnetin may protect from SARS-CoV-2 infection by reducing ACE2 |
| title_full | Daphnetin may protect from SARS-CoV-2 infection by reducing ACE2 |
| title_fullStr | Daphnetin may protect from SARS-CoV-2 infection by reducing ACE2 |
| title_full_unstemmed | Daphnetin may protect from SARS-CoV-2 infection by reducing ACE2 |
| title_short | Daphnetin may protect from SARS-CoV-2 infection by reducing ACE2 |
| title_sort | daphnetin may protect from sars cov 2 infection by reducing ace2 |
| topic | Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) Angiotensin-converting enzyme 2 (ACE2) Daphnetin (DAP) Prevention HIF-1α JAK2 |
| url | https://doi.org/10.1038/s41598-024-79734-z |
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