新型抗SARS-CoV-2药物苹果酸（±）-娃儿藤碱的发现及纳米制剂研究
Discovery and Nanosized Preparations of (,)-Tylophorine Malate as Novel anti-SARS-CoV-2 Agents.
作者信息
Wang Ziwen, Ye Fei, Feng Yue, Xiao Wen, Song Hongjian, Zhao Li, Lu Roujian, Huang Baoying, Liu Yuxiu, Wang Wenling, Li Yongqiang, Ding Yi, Zheng Yanlong, Song Xiangrong, Tan Wenjie, Wang Qingmin
机构信息
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, College of Chemistry, Frontiers Science Center for New Organic Matter, Nankai University, Tianjin 300071, China.
Tianjin Key Laboratory of Structure and Performance for Functional Molecules, College of Chemistry, Tianjin Normal University, Tianjin 300387, China.
出版信息
ACS Med Chem Lett. 2021 Oct 24;12(11):1838-1844. doi: 10.1021/acsmedchemlett.1c00481. eCollection 2021 Nov 11.
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has stimulated the search for effective drugs for its prevention and treatment. Natural products are an important source for new drug discovery. Here, we report that, NK007(,), a tylophorine malate, displays high antiviral activity against SARS-CoV-2 with an EC 0.03 μM , which is substantially lower than that of remdesivir (EC: 0.8 μM ), the only authorized drug to date. The histopathological research revealed that NK007(,) (5 mg/kg/dose) displayed a protection effect in lung injury induced by SARS-CoV-2, which is better than remdesivir (25 mg/kg/dose). We also prepared two nanosized preparations of NK007(,), which also showed good efficacy (EC: NP-NK007, 0.007 μM ; LP-NK007, 0.014 μM ). Our findings suggest that tylophora alkaloids, isolated from the traditional Chinese medicine offer a new skeleton for the development of anticoronavirus drug candidate.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的2019冠状病毒病（COVID-19）大流行激发了人们对其预防和治疗有效药物的探索。天然产物是新药发现的重要来源。在此，我们报告，一种马来酸娃儿藤碱NK007对SARS-CoV-2显示出高抗病毒活性，其半数有效浓度（EC）为0.03 μM，远低于目前唯一获批药物瑞德西韦的半数有效浓度（EC：0.8 μM）。组织病理学研究表明，NK007（5 mg/kg/剂量）对SARS-CoV-2诱导的肺损伤具有保护作用，优于瑞德西韦（25 mg/kg/剂量）。我们还制备了两种NK007纳米制剂，它们也显示出良好的疗效（EC：纳米颗粒NK007为0.007 μM；脂质体NK007为0.014 μM）。我们的研究结果表明，从传统中药中分离得到的娃儿藤生物碱为抗冠状病毒候选药物的开发提供了一个新的骨架。
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