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Discovery of a natural fluorescent probe targeting the Plasmodium falciparum cysteine protease falcipain-2

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The Plasmodium falciparum cysteine protease falcipain-2 (FP-2) is an attractive antimalarial target. Here, we discovered that the natural compound NP1024 is a nonpeptidic inhibitor of FP-2 with an IC50 value of 0.44 μmol L−1. The most exciting finding is that both in vitro and in vivo, NP1024 directly targets FP-2 in malaria parasite-infected erythrocytes as a natural fluorescent probe, thereby paving the way for an integration of malaria diagnosis and treatment.

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We thank Prof. Hua Xie (Shanghai Insitute of Materia Medica, Chinese Academy of Sciences) for expert technical assistance with the target location experiments using confocal microscopy; Prof. Jin Huang (East China University of Science and Technology) for the enzyme inhibition assays and the effect evaluation of NP1024 on degradation of hemoglobin by FP-2; Profs. Huaimin Zhu, Weiqing Pan, Heng Peng, and Weibin Guan (The Secondary Military Medical University) for sharing Plasmodium parasite strains and providing technical assistance with the in vitro culture of Plasmodium parasites; Xianwen Yang (Third Institute of Oceanography, State Oceanic Administration) for providing natural compounds used in this study; Drs. Troy J. Smillie and Ikhlas A. khan (National Center for Natural Products Research, the University of Mississippi) for in vitro anti-malarial assay; We also thankProf Hualiang Jiang and Eric Xu (Shanghai Insitute of Materia Medica) for their technological assistance and helpful suggestions. This work was supported by the National Key Research and Development Program (2016YFA0502304 to H.L), the National Natural Science Foundation of China (81825020), the National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program ", China (20187X09711002), the Fundamental Research Funds for the Central Universities, Special Program for Applied Research on Super Computation of the NSFC-Guangdong Joint Fund (the second phase) (Ul 501501), Professor of Chang Jiang Scholars Program (to W.Z.), and the Natural Science Foundation of Zhejiang Province (LY15H190007). Honglin Li is also sponsored by the National Program for Special Supports of Eminent Professionals and National Program for Support of Top-notch Young Professionals.

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Correspondence to Weidong Zhang or Honglin Li.

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Compliance and ethics The author(s) declare that they have no conflict of interest.

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Zhu, L., Shan, L., Zhu, J. et al. Discovery of a natural fluorescent probe targeting the Plasmodium falciparum cysteine protease falcipain-2. Sci. China Life Sci. (2020). https://doi.org/10.1007/s11427-019-1581-2

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  • falcipain-2
  • malaria diagnosis
  • antimalarial agent
  • acylated flavonol monoglycoside
  • fluorescent probe