Department of Epidemiology, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, M. Miyazaki Marg, Tajganj, Agra, India.
Department of Epidemiology, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, M. Miyazaki Marg, Tajganj, Agra, India.
Infect Genet Evol. 2018 Jun;60:58-65. doi: 10.1016/j.meegid.2018.02.013. Epub 2018 Feb 15.
Leprosy is a chronic infection of skin and nerve caused by Mycobacterium leprae. The treatment is based on standard multi drug therapy consisting of dapsone, rifampicin and clofazamine. The use of rifampicin alone or with dapsone led to the emergence of rifampicin-resistant Mycobacterium leprae strains. The emergence of drug-resistant leprosy put a hurdle in the leprosy eradication programme. The present study aimed to predict the molecular model of ribonucleotide reductase (RNR), the enzyme responsible for biosynthesis of nucleotides, to screen new drugs for treatment of drug-resistant leprosy. The study was conducted by retrieving RNR of M. leprae from GenBank. A molecular 3D model of M. leprae was predicted using homology modelling and validated. A total of 325 characters were included in the analysis. The predicted 3D model of RNR showed that the ϕ and φ angles of 251 (96.9%) residues were positioned in the most favoured regions. It was also conferred that 18 α-helices, 6 β turns, 2 γ turns and 48 helix-helix interactions contributed to the predicted 3D structure. Virtual screening of Food and Drug Administration approved drug molecules recovered 1829 drugs of which three molecules, viz., lincomycin, novobiocin and telithromycin, were taken for the docking study. It was observed that the selected drug molecules had a strong affinity towards the modelled protein RNR. This was evident from the binding energy of the drug molecules towards the modelled protein RNR (-6.10, -6.25 and -7.10). Three FDA-approved drugs, viz., lincomycin, novobiocin and telithromycin, could be taken for further clinical studies to find their efficacy against drug resistant leprosy.
麻风病是由麻风分枝杆菌引起的一种慢性皮肤和神经感染。其治疗基于包含氨苯砜、利福平、氯法齐明的标准多药物疗法。单独使用利福平或与氨苯砜联合使用导致了耐利福平麻风分枝杆菌菌株的出现。耐药性麻风病的出现给麻风病消除计划带来了障碍。本研究旨在预测负责核苷酸生物合成的核糖核苷酸还原酶（RNR）的分子模型，以筛选治疗耐药性麻风病的新药。该研究通过从 GenBank 检索麻风分枝杆菌的 RNR 进行。使用同源建模预测并验证了麻风分枝杆菌的分子 3D 模型。分析中包含了总共 325 个字符。预测的 RNR 3D 模型表明，251 个（96.9%）残基的 ϕ 和 φ 角位于最有利区域。还证实了 18 个α-螺旋、6 个β转角、2 个γ转角和 48 个螺旋-螺旋相互作用有助于预测的 3D 结构。对美国食品和药物管理局批准的药物分子进行虚拟筛选，共回收了 1829 种药物，其中 3 种药物，即林可霉素、新生霉素和泰利霉素，被用于对接研究。观察到所选药物分子与模型化蛋白 RNR 具有很强的亲和力。这从药物分子对模型化蛋白 RNR 的结合能（-6.10、-6.25 和-7.10）中可以明显看出。可以选择三种美国食品和药物管理局批准的药物，即林可霉素、新生霉素和泰利霉素，进行进一步的临床研究，以确定它们对耐药性麻风病的疗效。
