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

  • ACS Med Chem Lett. 2021 Oct 24;12(11):1838-1844. doi: 10.1021/acsmedchemlett.1c00481.
Ziwen Wang  1  2 ,  Fei Ye  3 ,  Yue Feng  4 ,  Wen Xiao  4 ,  Hongjian Song  1 ,  Li Zhao  3 ,  Roujian Lu  3 ,  Baoying Huang  3 ,  Yuxiu Liu  1 ,  Wenling Wang  3 ,  Yongqiang Li  1 ,  Yi Ding  1  5 ,  Yanlong Zheng  1 ,  Xiangrong Song  4 ,  Wenjie Tan  3 ,  Qingmin Wang  1
Affiliations
  • 1. 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.
  • 2. Tianjin Key Laboratory of Structure and Performance for Functional Molecules, College of Chemistry, Tianjin Normal University, Tianjin 300387, China.
  • 3. NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention, China CDC, Beijing 102206, China.
  • 4. Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
  • 5. Shijiazhuang Lvfeng Chemical Co., Ltd., Shijiazhuang 052560, China.
PMID: 34745429 DOI: 10.1021/acsmedchemlett.1c00481
Abstract

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.

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