Mossallam Shereen F, El-Mansoury Salwa A T, Tolba Mona M, Kohla Asmaa A, Khedr Safaa I
Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Department of Parasitology, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Saudi J Biol Sci. 2021 Apr;28(4):2491-2501. doi: 10.1016/j.sjbs.2021.01.050. Epub 2021 Feb 2.
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.
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 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.
[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。
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。
