Department of Chemistry, Atma Ram Sanatan Dharma College, University of Delhi, New Delhi, India.
Department of Chemistry, University of Delhi, Delhi, India.
J Biomol Struct Dyn. 2022 Mar;40(4):1607-1616. doi: 10.1080/07391102.2020.1832918. Epub 2020 Oct 19.
Chikungunya virus (CHIKV) belongs to the alpha virus and it's infection in humans causes fever, known as chikungunya fever (CHIKF). It is a sudden onset of fever and may affect humans badly. The mode of transmission to human occurs due to the biting of the mosquitoes. Till date, thousands of humans are affected from this virus throughout the world. As on date, no promising medicine or vaccine is available in the market to cure from this viral infection. Therefore, there is a need of promising candidate against the nsp3 of CHIKV. In the present work, a library of the compounds are designed based on the product obtained in a multi-component reaction. Then, the designed compounds are filtered based on binding energy against the nsp3 of CHIKV obtained using molecular docking. Further, to understand the interaction of nsp3 of CHIKV and screened compound, CMPD474, the molecular dynamics MD) simulations at different temperatures, that is, 300, 325, 350, 375, and 400 K is performed. The binding or the formation of the complex is studied through different trajectories obtained from MD simulations. The accurate information for the binding energy is determined by performing MM-GBSA calculations and the best inhibition was observed at 300 K as the change in free energy for the formation of the complex is -7.0523 kcal/mol.Communicated by Ramaswamy H. Sarma.
基孔肯雅热病毒（CHIKV）属于甲病毒科，感染人类后会引起发热，称为基孔肯雅热（CHIKF）。它是一种突发的发热，可能会对人类造成严重影响。病毒传播给人类的方式是蚊子的叮咬。迄今为止，全世界已有数千人感染了这种病毒。截至目前，市场上还没有针对这种病毒感染的有效药物或疫苗。因此，需要寻找有前途的 CHIKV nsp3 抑制剂。在目前的工作中，根据多组分反应得到的产物设计了一个化合物库。然后，根据分子对接得到的与 CHIKV nsp3 的结合能对设计的化合物进行筛选。进一步，为了了解 CHIKV 的 nsp3 与筛选出的化合物 CMPD474 的相互作用，在不同温度下（300、325、350、375 和 400 K）进行分子动力学（MD）模拟。通过从 MD 模拟中获得的不同轨迹研究结合或复合物的形成。通过进行 MM-GBSA 计算确定了结合能的准确信息，并且在 300 K 下观察到最佳抑制效果，因为复合物形成的自由能变化为-7.0523 kcal/mol。由 Ramaswamy H. Sarma 传达。
