Daphnetin may protect from SARS-CoV-2 infection by reducing ACE2

被引:1
作者
Yang, Qian-wen [1 ,2 ]
Yue, Chang-ling [1 ,2 ]
Chen, Meng [2 ,5 ]
Ling, Yun-yun [3 ]
Dong, Qi [2 ]
Zhou, Ying-xin [2 ,5 ]
Cao, Yin [2 ,5 ]
Ding, Yan-xia [2 ]
Zhao, Xu [2 ]
Huang, Hai [1 ]
Zhang, Zhao-huan [4 ]
Hu, Lei [2 ,5 ]
Xu, Xiao-hui [2 ,5 ]
机构
[1] Shanghai Univ, Sch Life Sci, Shanghai 200444, Peoples R China
[2] Wannan Med Coll, Sch Preclin Med, Wuhu 241002, Peoples R China
[3] Wannan Med Coll, Dept Chem, Wuhu 241002, Peoples R China
[4] Naval Med Univ, Changzheng Hosp, Dept Lab Med, Shanghai 200003, Peoples R China
[5] Wannan Med Coll, Anhui Prov Key Lab Basic Res & Transformat Age rel, Wuhu 241002, Peoples R China
来源
SCIENTIFIC REPORTS | 2024年 / 14卷 / 01期
基金
中国国家自然科学基金;
关键词
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); Angiotensin-converting enzyme 2 (ACE2); Daphnetin (DAP); Prevention; HIF-1; alpha; JAK2;
D O I
10.1038/s41598-024-79734-z
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-1 alpha 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.
引用
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页数:12
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