College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China.
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.
Toxins (Basel). 2019 Jun 30;11(7):379. doi: 10.3390/toxins11070379.
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 () with an IC50 value of 3.045 μM. In the in vivo antiplasmodial assay, LZ1 exerted a significant antimalarial activity against () in a dose- and a time- dependent manner. In addition, LZ1 exhibited anti-inflammatory effects and attenuated liver-function impairment during 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.
抗疟药物耐药性是一个巨大的全球性威胁。最近，抗菌肽 (AMPs) 作为一种新的抗疟药物来源正在出现。在这项研究中，从蛇 cathelicidin 中鉴定出一种具有抗疟活性的 AMP LZ1。在体外抗疟试验中，LZ1 对血期（）具有强烈的抑制作用，IC50 值为 3.045 μM。在体内抗疟试验中，LZ1 以剂量和时间依赖的方式对（）表现出显著的抗疟活性。此外，LZ1 在疟原虫感染过程中表现出抗炎作用并减轻肝功能损伤。此外，通过在红细胞中使用抑制糖酵解和氧化磷酸化的抑制剂，LZ1 通过选择性抑制丙酮酸激酶活性特异性抑制寄生虫感染红细胞中的三磷酸腺苷 (ATP) 产生。总之，本研究表明 LZ1 是一种有潜力的新型抗疟药物候选物。
