Munir Asma, Vedithi Sundeep Chaitanya, Chaplin Amanda K, Blundell Tom L
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
Front Genet. 2020 Sep 4;11:965. doi: 10.3389/fgene.2020.00965. eCollection 2020.
Tuberculosis (TB) and leprosy are mycobacterial infections caused by and respectively. These diseases continue to be endemic in developing countries where the cost of new medicines presents major challenges. The situation is further exacerbated by the emergence of resistance to many front-line antibiotics. A priority now is to design new antimycobacterials that are not only effective in combatting the diseases but are also less likely to give rise to resistance. In both these respects understanding the structure of drug targets in and is crucial. In this review we describe structure-guided approaches to understanding the impacts of mutations that give rise to antimycobacterial resistance and the use of this information in the design of new medicines.
结核病（TB）和麻风病分别由结核分枝杆菌和麻风分枝杆菌引起，属于分枝杆菌感染。在发展中国家，这些疾病仍然流行，新药成本构成了重大挑战。对许多一线抗生素产生耐药性的情况进一步加剧了这一局面。当前的一个优先事项是设计新的抗分枝杆菌药物，这些药物不仅能有效对抗疾病，而且产生耐药性的可能性较小。在这两个方面，了解结核分枝杆菌和麻风分枝杆菌中药物靶点的结构至关重要。在本综述中，我们描述了基于结构的方法，以了解导致抗分枝杆菌耐药性的突变的影响，以及如何在新药设计中利用这些信息。
