背景:由于麻风杆菌不能在体外生长,针对麻风分枝杆菌的抗菌素耐药性测试或评估新药的抗麻风活性仍然很困难。此外,通过传统药物开发过程开发一种新的麻风病药物在经济上并不吸引制药公司。因此,重新利用现有药物/批准的药物或其衍生物来测试它们的抗惰性效力是一个有前途的替代方案。这是一种在批准的药物分子中揭示不同药物和治疗特性的加速方法。
目的:本研究旨在探索替诺福韦等抗病毒药物的结合潜力,恩曲他滨,和拉米夫定(TEL)对麻风分枝杆菌的分子对接。
方法:当前的研究评估并证实了重新利用抗病毒药物如TEL(替诺福韦,恩曲他滨,和拉米夫定)通过转移BIOVIADS2017的图形窗口与来自麻风分枝杆菌的磷酸甘油酸变位酶gpm1的晶体结构(PDBID:4EO9)。利用智能最小化算法,蛋白质的能量减少,以实现稳定的局部极小构象。
结果:蛋白质和分子能量最小化方案产生了稳定的构型能量分子。蛋白质4EO9能量从14264.5kcal/mol降低至-17588.1kcal/mol。
结论:基于CHARMm算法的CDOCKER运行将所有三个分子(TEL)对接在4EO9蛋白结合口袋(麻风分枝杆菌)内。相互作用分析显示,替诺福韦具有比其他分子更好的结合分子,得分为-37.7297kcal/mol。
BACKGROUND: Since leprosy bacilli cannot grow in vitro, testing for antimicrobial resistance against Mycobacterium leprae or assessing the anti-leprosy activity of new drugs remains hard. Furthermore, developing a new leprosy drug through the traditional drug development process is not economically captivating for pharmaceutical companies. As a result, repurposing existing drugs/approved medications or their derivatives to test their anti-leprotic potency is a promising alternative. It is an accelerated method to uncover different medicinal and therapeutic properties in approved drug molecules.
OBJECTIVE: The study aims to explore the binding potential of anti-viral drugs such as Tenofovir, Emtricitabine, and Lamivudine (
TEL) against Mycobacterium leprae using molecular docking.
METHODS: The current study evaluated and confirmed the possibility of repurposing antiviral drugs such as
TEL (Tenofovir, Emtricitabine, and Lamivudine) by transferring the graphical window of the BIOVIA DS2017 with the Crystal Structure of a phosphoglycerate mutase gpm1 from Mycobacterium leprae (PDB ID: 4EO9). Utilizing the smart minimizer algorithm, the protein\'s energy was reduced in order to achieve a stable local minima conformation.
RESULTS: The protein and molecule energy minimization protocol generated stable configuration energy molecules. The protein 4EO9 energy was reduced from 14264.5 kcal/mol to -17588.1 kcal/mol.
CONCLUSIONS: The CHARMm algorithm-based CDOCKER run docked all three molecules (
TEL) inside the 4EO9 protein binding pocket (Mycobacterium leprae). The interaction analysis revealed that tenofovir had a better binding molecule with a score of - 37.7297 kcal/mol than the other molecules.