Daphnetin may protect from SARS-CoV-2 infection by reducing ACE2
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.
Authors
- Yanfei Ding (ORCID: https://orcid.org/0000-0002-3460-1344)
- Xiaohui Xu (ORCID: https://orcid.org/0000-0001-7608-4114)
- Qi Dong (ORCID: https://orcid.org/0000-0002-6192-1597)
- Zhaohuan Zhang (ORCID: https://orcid.org/0000-0001-6882-9761)
- Chang-Ling Yue
- Yingxin Zhou (ORCID: https://orcid.org/0000-0001-7541-7327)
- Qian-wen Yang
- Meng Chen (ORCID: https://orcid.org/0000-0002-2449-5904)
- Lei Hu (ORCID: https://orcid.org/0000-0001-5219-2874)
- Xu Zhao (ORCID: https://orcid.org/0000-0002-3266-0148)
- Hai Huang (ORCID: https://orcid.org/0000-0002-5224-9911)
- Yinghui Ling (ORCID: https://orcid.org/0000-0003-1375-6440)
- Yin Cao
Institutions
- Wannan Medical College (CN)
- Shanghai University (CN)
Publication Details
- Journal
- Scientific Reports
- Published
- 2024-12-28
- DOI
- https://doi.org/10.1038/s41598-024-79734-z
- Citations
- 3
- Primary Topic
- Computational Drug Discovery Methods
- Type
- article
- Field-Weighted Citation Impact
- 1.08
Funders
- National Natural Science Foundation of China
- Wannan Medical College
- Natural Science Foundation of Anhui Province