Machaba Kgothatso E, Mhlongo Ndumiso N, Dokurugu Yussif M, Soliman Mahmoud Es
Molecular Modelling & Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4001, South Africa.
School of Laboratory Medicine & Medical Sciences, University of KwaZulu-Natal, Durban 4001, South Africa.
Future Med Chem. 2017 Jun;9(10):1055-1071. doi: 10.4155/fmc-2017-0020. Epub 2017 Jun 20.
Virtual screening (VS) is powerful tool in discovering molecular inhibitors that are most likely to bind to drug targets of interest. Herein, we introduce a novel VS approach, so-called 'tailored-pharmacophore', in order to explore inhibitors that overcome drug resistance. Methodology & results: The emergence and spread of drug resistance strains of tuberculosis is one of the most critical issues in healthcare. A tailored-pharmacophore approach was found promising to identify in silico predicted hit with better binding affinities in case of the resistance mutations in MtbHadAB as compared with thiacetazone, a prodrug used in the clinical treatment of tuberculosis.
This approach can potentially be enforced for the discovery and design of drugs against a wide range of resistance targets.
虚拟筛选（VS）是发现最有可能与感兴趣的药物靶点结合的分子抑制剂的有力工具。在此，我们引入一种新型的虚拟筛选方法，即所谓的“定制药效团”，以探索克服耐药性的抑制剂。
结核耐药菌株的出现和传播是医疗保健中最关键的问题之一。与临床治疗结核病中使用的前药硫代乙酰胺相比，定制药效团方法有望在结核分枝杆菌HadAB发生耐药突变的情况下，在计算机模拟预测中识别出具有更好结合亲和力的命中靶点。
这种方法有可能用于发现和设计针对广泛耐药靶点的药物。
