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

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

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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-N10118
    SARS-CoV Inhibitor