a Department of Pharmacognosy and Phytochemistry , B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre , Ahmedabad , Gujarat , India.
b Registered Ph.D. student of Gujarat University , Ahmedabad , Gujarat , India.
J Biomol Struct Dyn. 2019 Aug;37(12):3150-3161. doi: 10.1080/07391102.2018.1509732. Epub 2018 Dec 28.
The transmission of mosquito-borne Chikungunya virus (CHIKV) has large epidemics worldwide. Till date, there are neither anti-viral drugs nor vaccines available for the treatment of Chikungunya. Accumulated evidences suggest that some natural compounds i.e., Epigallocatechin gallate, Harringtonine, Apigenin, Chrysin, Silybin, etc. have the capability to inhibit CHIKV replication . Natural compounds are known to possess less or no side effects. Therefore, natural compound in its purified or crude extracts form could be the preeminent and safe mode of therapies for Chikungunya. Wet lab screening and identification of natural compounds against Chikungunya targets is a time consuming and expensive exercise. In the present study, we used techniques like receptor-ligand docking, Molecular dynamic (MD), Three Dimensional Quantitative Structure Activity Relation (3D-QSAR) and ADME properties to screen out potential compounds. Aim of the study is to identify potential lead/s from natural sources using techniques that can be developed as a drug like molecule against Chikungunya infection and replication. Three softwares were used for molecular docking studies. Potential ligands selected by docking studies were subsequently subjected 3D-QSAR studies to predict biological activity. Based on docking scores and pIC value, potential anti-Chikungunya compounds were identified. Best docked receptor-ligands were also subjected to MD for more accurate estimation. Lipinski's rule and ADME studies of the identified compounds were also studied to assess their drug likeness properties. Results of findings, led to identification of few best fit compounds of natural origin against targets of Chikungunya virus which may lead to discovery of new drugs for Chikungunya. Communicated by Ramaswamy H. Sarma.
虫媒基孔肯雅病毒（CHIKV）的传播在全球范围内引发了大规模的疫情。迄今为止，尚无针对基孔肯雅热的抗病毒药物或疫苗。有大量证据表明，一些天然化合物，如表没食子儿茶素没食子酸酯、高三尖杉酯碱、芹菜素、白杨素、水飞蓟素等，具有抑制 CHIKV 复制的能力。天然化合物的副作用较小或没有。因此，天然化合物的纯化或粗提物形式可能是基孔肯雅热治疗的卓越和安全模式。在实验室筛选和鉴定针对基孔肯雅目标的天然化合物是一项耗时且昂贵的工作。在本研究中，我们使用了受体-配体对接、分子动力学（MD）、三维定量构效关系（3D-QSAR）和 ADME 特性等技术进行筛选。本研究的目的是使用可以开发成针对基孔肯雅感染和复制的药物样分子的技术，从天然来源中识别潜在的先导化合物。使用了三种软件进行分子对接研究。通过对接研究选择的潜在配体随后进行 3D-QSAR 研究，以预测生物活性。基于对接评分和 pIC 值，确定了潜在的抗基孔肯雅化合物。最佳对接的受体-配体也进行了 MD 模拟，以进行更准确的估计。还研究了鉴定化合物的 Lipinski 规则和 ADME 特性，以评估它们的药物相似性。研究结果确定了几种针对基孔肯雅病毒靶标的最佳天然来源拟合化合物，这可能会发现针对基孔肯雅的新药物。由 Ramaswamy H. Sarma 传达。
