Singh Ankita, Mina Usha, Yadav Pardeep
School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
J Ayurveda Integr Med. 2025 Jul-Aug;16(4):101158. doi: 10.1016/j.jaim.2025.101158. Epub 2025 Jun 27.
Tuberculosis remains a pervasive and enduring global health challenge, with the alarming rise of drug-resistant variants. Mycobacterium tuberculosis (M. tuberculosis), bacterium responsible for tuberculosis, deploys a complex arsenal of virulence factors to evade the host's immune defences. The quest for novel targets or compounds to combat drug-resistant M. tuberculosis strains is of paramount importance. PanK is an essential enzyme for Co-enzyme A (CoA) biosynthesis pathway, targeting inhibition of its activity by Withania somnifera phytochemicals may provide an effective therapeutic strategy against resistant strains.
The study aims to identify the potential of natural compounds derived from Withania somnifera as inhibitors of the PanK enzyme (novel target) in M. tuberculosis.
In silico computational approach, includes steps-structure based virtual screening of 83 Withania compounds followed by molecular docking and dynamic simulations spanning 100 ns, to assess the binding affinity and stability between screen key compounds and PanK. In vitro anti-tuberculosis bioassays was also performed to validate the In silico experiments finding.
Through in silico experiments, four key compounds of Withania somnifera were -Morkotin A, Rutin, Withaoxylactone, and 2,3-Dihydrowithanolide E were identified. They exhibited strong potential to inhibit PanK enzyme activity. The In silico as well as In vitro findings suggest that Withania somnifera-derived natural compounds could serve as effective candidates for targeting vital enzymes in M. tuberculosis.
Withania somnifera can be explored as valuable resource for developing novel drugs for PanK as a target to combat tuberculosis.
结核病仍然是一个普遍且持久的全球健康挑战，耐药变种的数量惊人地增加。导致结核病的结核分枝杆菌利用一系列复杂的毒力因子来逃避宿主的免疫防御。寻找对抗耐药结核分枝杆菌菌株的新靶点或化合物至关重要。泛酸激酶是辅酶A（CoA）生物合成途径中的一种必需酶，靶向抑制其活性的睡茄植物化学物质可能提供一种对抗耐药菌株的有效治疗策略。
本研究旨在确定来自睡茄的天然化合物作为结核分枝杆菌中泛酸激酶酶（新靶点）抑制剂的潜力。
采用计算机模拟计算方法，包括基于结构的虚拟筛选83种睡茄化合物，随后进行分子对接和跨度为100纳秒的动态模拟，以评估筛选出的关键化合物与泛酸激酶之间的结合亲和力和稳定性。还进行了体外抗结核生物测定以验证计算机模拟实验结果。
通过计算机模拟实验，确定了睡茄的四种关键化合物——莫尔可亭A、芦丁、睡茄内酯和2,3-二氢睡茄醇内酯E。它们表现出很强的抑制泛酸激酶酶活性的潜力。计算机模拟以及体外实验结果表明，来自睡茄的天然化合物可作为靶向结核分枝杆菌中重要酶的有效候选物。
睡茄可作为开发以泛酸激酶为靶点的新型抗结核药物的宝贵资源进行探索。
