Medicinal Chemistry Research Laboratory, MNR College of Pharmacy, Sangareddy, Hyderabad, India.
Department of Pharmacy, BITS, Pilani, Pilani, Rajasthan, India.
J Biomol Struct Dyn. 2023 Dec;41(20):10678-10689. doi: 10.1080/07391102.2023.2188428. Epub 2023 Mar 11.
Monkeypox is a zoonotic viral disease that mainly affects tropical rainforest regions of central and west Africa, with sporadic exportations to other places. Since there is no cure, treating monkeypox with an antiviral drug developed for smallpox is currently acceptable. Our study mainly focused on finding new therapeutics to target monkeypox from existing compounds or medications. It is a successful method for discovering or developing medicinal compounds with novel pharmacological or therapeutic applications. In this study, homology modelling developed the Monkeypox TMPK (IMNR) structure. Ligand-based pharmacophore was generated using the best docking pose of standard ticovirimat. Further, molecular docking analysis showed compounds, tetrahydroxycurcumin, procyanidin, rutin, vicenin-2, kaempferol 3-(6''-malonylglucoside) were the top five binding energy compounds against TMPK (1MNR). Furthermore, we carried out MD simulations for 100 ns for the six compounds, including reference based on the binding energies and interactions. MD studies revealed that as ticovirimat interacted with residues Lys17, Ser18, and Arg45, all the above five compounds interacted with the same amino acids at the active site during docking and simulation studies. Among all the compounds, ZINC4649679 (Tetrahydroxycurcumin) was shown to have the highest binding energy -9.7 kcal/mol and also observed stable protein-ligand complex during MD studies. ADMET profile estimation showed that the docked phytochemicals were safe. However, further biological assessment through a wet lab is essential to measure the efficacy and safety of the compounds.Communicated by Ramaswamy H. Sarma.
猴痘是一种由动物传染给人类的正痘病毒疾病，主要影响中非和西非的热带雨林地区，偶尔也会传播到其他地方。由于目前尚无治愈方法，用针对天花开发的抗病毒药物治疗猴痘是可以接受的。我们的研究主要集中在寻找针对猴痘的新疗法，从现有化合物或药物中寻找。这是一种成功的方法，可以发现或开发具有新的药理或治疗应用的药用化合物。在这项研究中，同源建模开发了猴痘 TMPK（IMNR）结构。基于配体的药效团是使用标准替科维马的最佳对接构象生成的。此外，分子对接分析表明，化合物四羟基姜黄素、原花青素、芦丁、vicenin-2、山奈酚 3-(6''-丙二酰葡萄糖苷)是针对 TMPK（1MNR）的前五名结合能化合物。此外，我们对 6 种化合物（包括基于结合能和相互作用的参考化合物）进行了 100ns 的 MD 模拟。MD 研究表明，替科维马与残基 Lys17、Ser18 和 Arg45 相互作用，所有上述 5 种化合物在对接和模拟研究中与活性位点的相同氨基酸相互作用。在所有化合物中，ZINC4649679（四羟基姜黄素）表现出最高的结合能-9.7 kcal/mol，并且在 MD 研究中也观察到稳定的蛋白-配体复合物。ADMET 概况估计表明，对接的植物化学物质是安全的。然而，通过湿实验室进一步进行生物评估对于测量化合物的功效和安全性是必要的。由 Ramaswamy H. Sarma 传达。
