Khan Mahvish, Khan Saif, Bushara Nashwa Zaki Ali, Ali Rafat, Tabassum Zainab, Ishrat Romana, Marouf Hussein Abdel-Aziz, Sherwani Subuhi, Mirza Shadab, Haque Shafiul
Department of Biology, College of Science, Ha'il University, Ha'il, Saudi Arabia.
Department of Basic Dental and Medical Sciences, College of Dentistry, Ha'il University, Ha'il, Saudi Arabia.
J Biomol Struct Dyn. 2023;41(23):13857-13872. doi: 10.1080/07391102.2023.2193992. Epub 2023 Apr 17.
Leprosy is a chronic infectious disease caused by a bacillus, Mycobacterium leprae. According to official data from 139 countries in the 6 WHO Regions, there were 127558 new leprosy cases worldwide in 2020. Leprosy mainly affects the skin, the peripheral nerves, mucosa of the upper respiratory tract, and the eyes. If this disease is left untreated, can harm the skin, nerves, limbs, eyes, and skin permanently. The disease is curable with multidrug therapy. Over a period of time Mycobacterium leprae has become resistant to these drugs. Therefore, new therapeutic molecules are warranted. This study was aimed to carry out the in-silico analysis to determine the inhibitory effect of natural compounds on Dihydropteroate synthase (DHPS) of The DHPS is a key enzyme in the folate biosynthesis pathway in and acts as a competitive inhibitor of PABA. The 3D structure of DHPS protein was modeled using homology modeling and was validated. Molecular docking and simulation along with other in-silico methods were employed to determine the inhibitory effect of ligand molecules towards DHPS target protein. Results revealed ZINC03830554 molecule as a potential inhibitor of DHPS. Binding experiments and bioassays utilizing this strong inhibitor molecule against purified DHPS protein are necessary to validate these early findings.Communicated by Ramaswamy H. Sarma.
麻风病是由一种杆菌——麻风分枝杆菌引起的慢性传染病。根据世界卫生组织6个区域139个国家的官方数据，2020年全球有127558例新的麻风病病例。麻风病主要影响皮肤、周围神经、上呼吸道黏膜和眼睛。如果这种疾病不治疗，会对皮肤、神经、四肢、眼睛造成永久性伤害。这种疾病可用多药疗法治愈。一段时间以来，麻风分枝杆菌已对这些药物产生耐药性。因此，需要新的治疗分子。本研究旨在进行计算机模拟分析，以确定天然化合物对麻风分枝杆菌二氢蝶酸合酶（DHPS）的抑制作用。DHPS是麻风分枝杆菌叶酸生物合成途径中的关键酶，可作为对氨基苯甲酸（PABA）的竞争性抑制剂。利用同源建模对DHPS蛋白的三维结构进行建模并验证。采用分子对接和模拟以及其他计算机模拟方法来确定配体分子对DHPS靶蛋白的抑制作用。结果显示ZINC03830554分子是DHPS的潜在抑制剂。利用这种强效抑制剂分子对纯化的DHPS蛋白进行结合实验和生物测定，对于验证这些早期发现是必要的。由拉马斯瓦米·H·萨尔马传达。
