2. Academic Validation
  3. In Vitro and In Vivo Antimalarial Activity of LZ1, a Peptide Derived from Snake Cathelicidin

In Vitro and In Vivo Antimalarial Activity of LZ1, a Peptide Derived from Snake Cathelicidin

  • Toxins (Basel). 2019 Jun 30;11(7):379. doi: 10.3390/toxins11070379.
Yaqun Fang 1,  Xiaoqin He 2,  Pengcheng Zhang 1,  Chuanbin Shen 3,  James Mwangi 3,  Cheng Xu 3,  Guoxiang Mo 1,  Ren Lai 4 5,  Zhiye Zhang 6
Affiliations

Affiliations

  • 1 College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China.
  • 2 Key Laboratory of National Health and Family Planning Commission on Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi 214064, China.
  • 3 Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, Kunming Institute of Zoology, Kunming 650223, China.
  • 4 College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China. rlai72@njau.edu.cn.
  • 5 Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, Kunming Institute of Zoology, Kunming 650223, China. rlai72@njau.edu.cn.
  • 6 Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, Kunming Institute of Zoology, Kunming 650223, China. zhangzhiye@mail.kiz.ac.cn.
PMID: 31262018 DOI: 10.3390/toxins11070379
Abstract

Antimalarial drug resistance is an enormous global threat. Recently, Antimicrobial Peptides (AMPs) are emerging as a new source of antimalarials. In this study, an AMP LZ1 derived from snake cathelicidin was identified with antimalarial activity. In the in vitro antiplasmodial assay, LZ1 showed strong suppression of blood stage Plasmodium falciparum (P. falciparum) with an IC50 value of 3.045 μM. In the in vivo antiplasmodial assay, LZ1 exerted a significant antimalarial activity against Plasmodium berghei (P. berghei) in a dose- and a time- dependent manner. In addition, LZ1 exhibited anti-inflammatory effects and attenuated liver-function impairment during P. berghei Infection. Furthermore, by employing inhibitors against glycolysis and Oxidative Phosphorylation in erythrocytes, LZ1 specifically inhibited adenosine triphosphate (ATP) production in parasite-infected erythrocyte by selectively inhibiting the Pyruvate Kinase activity. In conclusion, the present study demonstrates that LZ1 is a potential candidate for novel antimalarials development.

Keywords

ATP; antimicrobial peptide; cytokine; malaria; pyruvate kinase.

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