V.M.K.V. Engineering College, Department of Bioinformatics , Salem 636308, Tamil Nadu , India.
Expert Opin Drug Discov. 2013 Oct;8(10):1239-51. doi: 10.1517/17460441.2013.826188. Epub 2013 Aug 7.
Leprosy is a slowly progressing bacterial infection caused by Mycobacterium leprae. The World Health Organization recommended multidrug therapy (MDT) which is extremely effective and halts the progress of the disease. Even though the objective of eliminating leprosy as a public health problem has been achieved successfully, leprosy is not yet eradicated. Furthermore, the long-term use of MDT results in single- and multidrug resistance. Therefore, there is still a need for new drug discovery for leprosy.
The authors explain the importance of discovery of new drug to leprosy and the significance of homology modeling to drug discovery. This review highlights the principle steps, applications, and the resources of homology modeling. Finally, the authors emphasize the application of different structure-based drug design (SBDD) approaches to design novel therapeutics for leprosy.
MDT has proved to be effective in controlling infection, with prevalence of leprosy now predominantly isolated to the developing countries. The emergence of single- and multidrug-resistant strains of M. leprae has, however, provided some concern with the need for newer antibacterial agents. Drug resistance can be overcome by multi-targeted therapy. SBDD approaches, which reported many successful drugs, depend predominantly on the three-dimensional (3D) structure of drug targets. As of 2013, only very few experimental structures are available for M. leprae proteins. Hence, SBDD, in leprosy research, relies heavily on homology modeling to predict the 3D structure of drug targets and to design better therapeutics.
麻风病是一种由麻风分枝杆菌引起的缓慢进展的细菌性感染。世界卫生组织推荐使用多药疗法（MDT），这种疗法非常有效，可以阻止疾病的进展。尽管成功地实现了将麻风病作为一个公共卫生问题消除的目标，但麻风病尚未被根除。此外，MDT 的长期使用导致了单药和多药耐药性。因此，仍然需要发现治疗麻风病的新药。
作者解释了发现治疗麻风病新药的重要性以及同源建模对药物发现的意义。这篇综述强调了同源建模的原则步骤、应用和资源。最后，作者强调了不同结构为基础的药物设计（SBDD）方法在设计新型麻风病治疗方法中的应用。
MDT 已被证明在控制感染方面非常有效，现在麻风病的流行主要局限于发展中国家。然而，麻风分枝杆菌单药和多药耐药株的出现引起了一些关注，需要新的抗菌药物。多靶点治疗可以克服耐药性。SBDD 方法报告了许多成功的药物，主要依赖于药物靶点的三维（3D）结构。截至 2013 年，只有极少数实验结构可用于麻风分枝杆菌蛋白。因此，SBDD 在麻风病研究中严重依赖同源建模来预测药物靶点的 3D 结构，并设计更好的治疗方法。
