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Discovery and Nanosized Preparations of (S,R)‑Tylophorine Malate as Novel anti-SARS-CoV‑2 Agents

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journal contribution
posted on 24.10.2021, 14:13 by Ziwen Wang, Fei Ye, Yue Feng, Wen Xiao, Hongjian Song, Li Zhao, Roujian Lu, Baoying Huang, Yuxiu Liu, Wenling Wang, Yongqiang Li, Yi Ding, Yanlong Zheng, Xiangrong Song, Wenjie Tan, Qingmin Wang
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(S,R), a tylophorine malate, displays high antiviral activity against SARS-CoV-2 with an EC50 0.03 μM in vitro, which is substantially lower than that of remdesivir (EC50: 0.8 μM in vitro), the only authorized drug to date. The histopathological research revealed that NK007­(S,R) (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(S,R), which also showed good efficacy (EC50: NP-NK007, 0.007 μM in vitro; LP-NK007, 0.014 μM in vitro). Our findings suggest that tylophora alkaloids, isolated from the traditional Chinese medicine Cynanchum komarovii AL, offer a new skeleton for the development of anticoronavirus drug candidate.