人亚型对西米普明的体外敏感性。
In vitro susceptibility of human subtypes to simeprevir.
作者信息
Mossallam Shereen F, El-Mansoury Salwa A T, Tolba Mona M, Kohla Asmaa A, Khedr Safaa I
机构信息
Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Department of Parasitology, Medical Research Institute, Alexandria University, Alexandria, Egypt.
出版信息
Saudi J Biol Sci. 2021 Apr;28(4):2491-2501. doi: 10.1016/j.sjbs.2021.01.050. Epub 2021 Feb 2.
INTRODUCTION AND AIM
is a common enteric parasite, having a worldwide distribution. Many antimicrobial agents are effective against it, yet side effects and drug resistance have been reported. Thus, ongoing trials are being conducted for exploring anti- alternatives. Proteases are attractive anti-protozoal drug targets, having documented roles in . Serine proteases are present in both hepatitis C virus and . Since drug repositioning is quite trendy, the efficacy of simeprevir (SMV), an anti-hepatitis serine protease inhibitor, against was investigated in the current study.
METHODS
Stool samples were collected from patients, Alexandria, Egypt. Concentrated stools were screened using direct smears, trichrome, and modified Ziehl-Neelsen stains to exclude parasitic co-infections. Positive stool isolates were cultivated, molecularly subtyped for assessing the efficacy of three SMV doses (100,150, and 200 μg/ml) along 72 hours (h), on the most common subtype, through monitoring parasite growth, viability, re-culture, and also via ultrastructure verification. The most efficient dose and duration were later tested on other subtypes.
RESULTS
Results revealed that was detected in 54.17% of examined samples. Molecularly, ST3 predominated (62%), followed by ST1 (8.6%) and ST2 (3.4%). Ascending concentrations of SMV progressively inhibited growth, viability, and re-culture of treated , with a non-statistically significant difference when compared to the therapeutic control metronidazole (MTZ). The most efficient dose and duration against ST3 was 150 µg/ml for 72 h. This dose inhibited the growth of ST3, ST1, and ST2 with percentages of 95.19%, 94.83%, and 94.74%, successively and viability with percentages of 98.30%, 98.09%, and 97.96%, successively. This dose abolished upon re-culturing. Ultra-structurally, SMV induced rupture of cell membrane leading to necrotic death, versus the reported apoptotic death caused by MTZ. In conclusion, 150 µg/ml SMV for 72 h proved its efficacy against ST1, ST2, and ST3 , thus sparing the need for pre-treatment molecular subtyping in developing countries.
引言与目的
[寄生虫名称]是一种常见的肠道寄生虫，在全球范围内均有分布。许多抗菌药物对其有效，但也有副作用和耐药性的报道。因此，正在进行相关试验以探索抗寄生虫的替代药物。蛋白酶是有吸引力的抗原生动物药物靶点，在[相关生理过程]中发挥着已被证实的作用。丝氨酸蛋白酶在丙型肝炎病毒和[另一相关病毒或病原体]中均有存在。由于药物重新定位很流行，本研究考察了抗丙型肝炎丝氨酸蛋白酶抑制剂simeprevir（SMV）对[寄生虫名称]的疗效。
方法
从埃及亚历山大市的患者中收集粪便样本。对浓缩粪便进行直接涂片、三色染色和改良齐-尼氏染色筛查，以排除寄生虫合并感染。对阳性粪便分离株进行培养，对最常见的亚型进行分子分型，通过监测寄生虫生长、活力、再培养情况以及超微结构验证，评估三种SMV剂量（100、150和200μg/ml）在72小时内的疗效。随后对其他亚型测试最有效的剂量和持续时间。
结果
结果显示，在所检测的样本中，54.17%检测到[寄生虫名称]。分子层面上，ST3占主导（62%），其次是ST1（8.6%）和ST2（3.4%）。随着SMV浓度升高，逐渐抑制了经处理的[寄生虫名称]的生长、活力和再培养能力，与治疗对照甲硝唑（MTZ）相比，差异无统计学意义。针对ST3最有效的剂量和持续时间是150μg/ml作用72小时。该剂量依次抑制ST3、ST1和ST2生长的百分比分别为95.19%、94.83%和94.74%，抑制活力的百分比分别为98.30%、98.09%和97.96%。该剂量在再培养时使[寄生虫名称]失活。超微结构方面，SMV导致[寄生虫名称]细胞膜破裂，引发坏死性死亡，而MTZ导致的是凋亡性死亡。总之，150μg/ml SMV作用72小时证明了其对ST1、ST2和ST3[寄生虫名称]的疗效，因此在发展中国家无需进行治疗前的分子分型。
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