Yang Qian-Wen, Yue Chang-Ling, Chen Meng, Ling Yun-Yun, Dong Qi, Zhou Ying-Xin, Cao Yin, Ding Yan-Xia, Zhao Xu, Huang Hai, Zhang Zhao-Huan, Hu Lei, Xu Xiao-Hui
School of Life Sciences, Shanghai University, Shanghai, 200444, China.
School of Preclinical Medicine, Wannan Medical College, Wuhu, 241002, China.
Sci Rep. 2024 Dec 28;14(1):30682. doi: 10.1038/s41598-024-79734-z.
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.
为抗击新型冠状病毒肺炎疫情，需要创新的预防策略，包括降低呼吸道细胞上血管紧张素转换酶2（ACE2）的表达。本研究筛选了中国已批准的药物下调ACE2的能力。发现瑞香素（DAP）可显著降低PC9细胞中ACE2的mRNA和蛋白质水平。DAP通过靶向缺氧诱导因子-1α（HIF-1α）和Janus激酶2（JAK2）对ACE2表达发挥抑制作用，从而阻碍ACE2基因的转录。新型冠状病毒假病毒感染试验证实，经DAP处理的PC9细胞对病毒感染的易感性降低。在治疗剂量下，DAP可有效降低小鼠和人类呼吸系统中ACE2的表达。这表明，已被批准用于其他病症的DAP可能是一种预防新型冠状病毒的新措施，为减少新型冠状病毒传播提供了一种经济有效且易于获得的方法。
