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

tetano

Editor, Senior Moderator
Sci Rep


. 2024 Dec 28;14(1):30682.
doi: 10.1038/s41598-024-79734-z. Daphnetin may protect from SARS-CoV-2 infection by reducing ACE2

Qian-Wen Yang[SUP] #[/SUP][SUP] 1 2 [/SUP], Chang-Ling Yue[SUP] #[/SUP][SUP] 1 2 [/SUP], Meng Chen[SUP] #[/SUP][SUP] 2 3 [/SUP], Yun-Yun Ling[SUP] 4 [/SUP], Qi Dong[SUP] 2 [/SUP], Ying-Xin Zhou[SUP] 2 3 [/SUP], Yin Cao[SUP] 2 3 [/SUP], Yan-Xia Ding[SUP] 2 [/SUP], Xu Zhao[SUP] 2 [/SUP], Hai Huang[SUP] 1 [/SUP], Zhao-Huan Zhang[SUP] 5 [/SUP], Lei Hu[SUP] 6 7 [/SUP], Xiao-Hui Xu[SUP] 8 9 [/SUP]



Affiliations
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.

Keywords: Angiotensin-converting enzyme 2 (ACE2); Daphnetin (DAP); HIF-1α; JAK2; Prevention; Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2).

 
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