PDF(Pubmed)
Abstract：
Parasitic diseases, predominantly prevalent in developing countries, are increasingly spreading to high-income nations due to shifting migration patterns. The World Health Organization (WHO) estimates approximately 300 million annual cases of giardiasis. The emergence of drug resistance and associated side effects necessitates urgent research to address this growing health concern. In this study, we evaluated over eleven thousand pharmacological compounds sourced from the FDA database to assess their impact on the TATA-binding protein (TBP) of the early diverging protist Giardia lamblia, which holds medical significance. We identified a selection of potential pharmacological compounds for combating this parasitic disease through in silico analysis, employing molecular modeling techniques such as homology modeling, molecular docking, and molecular dynamics simulations. Notably, our findings highlight compounds DB07352 and DB08399 as promising candidates for inhibiting the TBP of Giardia lamblia. Also, these compounds and DB15584 demonstrated high efficacy against trophozoites in vitro. In summary, this study identifies compounds with the potential to combat giardiasis, offering the prospect of specific therapies and providing a robust foundation for future research.
摘要：
寄生虫病,主要在发展中国家流行，由于移民模式的转变，越来越多地蔓延到高收入国家。世界卫生组织（WHO）估计每年约有3亿例贾第鞭毛虫病病例。耐药性和相关副作用的出现需要紧急研究来解决这一日益增长的健康问题。在这项研究中,我们评估了来自FDA数据库的超过一万一千种药理化合物，以评估它们对早期分化的长柄贾第鞭毛虫TATA结合蛋白（TBP）的影响，这具有医学意义。我们通过计算机分析确定了一些潜在的药物化合物来对抗这种寄生虫病，采用分子建模技术，如同源建模，分子对接,和分子动力学模拟。值得注意的是,我们的研究结果强调了化合物DB07352和DB08399是抑制蓝氏贾第鞭毛虫TBP的有希望的候选化合物。此外，这些化合物和DB15584在体外表现出对滋养体的高效。总之,这项研究确定了具有对抗贾第鞭毛虫病潜力的化合物，提供特定疗法的前景，并为未来的研究提供坚实的基础。
