The eradication of leprosy: molecular modeling techniques for novel drug discovery

Abstract

Introduction: 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.Areas covered: 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.Expert opinion: 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.