Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan.
Department of Biotechnology, Sona College of Arts and Science, Salem India.
J Biomol Struct Dyn. 2022 Aug;40(13):5769-5784. doi: 10.1080/07391102.2021.1873190. Epub 2021 Jan 25.
The unavailability of vaccine and medicines raised serious issues during COVID-19 pandemic and peoples from different parts of world relied on traditional medicine for their immediate recovery from COVID-19 and it found effective also. The current research aims to target COVID-19 immunological human host receptors i.e. angiotensin-converting enzyme (ACE)-2, interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α) and protease-activated receptor (PAR)-1 using curcumin derivatives to prevent viral infection and control overproduction of early clinical responses of COVID-19. Targeting these host proteins will mitigate the infection and will filter out many complications caused by these proteins in COVID-19 patients. It is proven through computer-aided computational modeling approaches, total 30 compounds of curcumin and its derivatives were chosen. Drug-likeness parameters were calculated for curcumin and its derivatives and 20 curcumin analogs were selected for docking analysis. From docking analysis of 20 curcumin analogs against five chosen human host receptor targets reveals 11 curcumin analogs possess least binding affinity and best interaction at active sites subjected to absorption, distribution, metabolism, excretion (ADME) analysis. Density functional theory (DFT) analysis of five final shortlisted curcumin derivatives was done to show least binding affinity toward chosen host target protein. Molecular dynamics simulation (MDS) was performed to observe behavior and interaction of potential drug hydrazinocurcumin against target proteins ACE-2 and PAR-1. It was performed at 100 nanoseconds and showed satisfactory results. Finally, our investigation reveals that hydrazinocurcumin possesses immunomodulatory and anti-cytokine therapeutic potential against COVID-19 and it can act as COVID-19 warrior drug molecule and promising choice of drug for COVID-19 treatment, however, it needs further clinical evaluation to commercialize as COVID-19 drug.Communicated by Ramaswamy H. Sarma.
在 COVID-19 大流行期间，疫苗和药品的缺乏引发了严重问题，来自世界不同地区的人们依赖传统医学来从 COVID-19 中迅速康复，并且发现传统医学也很有效。目前的研究旨在针对 COVID-19 免疫宿主受体，即血管紧张素转化酶 (ACE)-2、白细胞介素 (IL)-1β、IL-6、肿瘤坏死因子-α (TNF-α) 和蛋白酶激活受体 (PAR)-1，使用姜黄素衍生物来预防病毒感染并控制 COVID-19 的早期临床反应过度产生。针对这些宿主蛋白将减轻感染，并滤除 COVID-19 患者由这些蛋白引起的许多并发症。通过计算机辅助计算建模方法证明，选择了姜黄素及其 30 种衍生物。计算了姜黄素及其衍生物的药物相似性参数，并选择了 20 种姜黄素类似物进行对接分析。从对五个选定的人类宿主受体靶标的 20 种姜黄素类似物的对接分析中，揭示了 11 种姜黄素类似物在活性部位具有最小的结合亲和力和最佳的相互作用，这些类似物经过吸收、分布、代谢和排泄 (ADME) 分析。对五个最终选定的姜黄素衍生物进行了密度泛函理论 (DFT) 分析，以显示对所选宿主靶蛋白的最小结合亲和力。进行了分子动力学模拟 (MDS)，以观察潜在药物肼基姜黄素对靶蛋白 ACE-2 和 PAR-1 的行为和相互作用。它在 100 纳秒内进行，结果令人满意。最后，我们的研究表明，肼基姜黄素具有针对 COVID-19 的免疫调节和抗细胞因子治疗潜力，可作为 COVID-19 战疫药物分子，是治疗 COVID-19 的有前途的药物选择，但是，它需要进一步的临床评估才能实现商业化作为 COVID-19 药物。由 Ramaswamy H. Sarma 传达。
