Abstract

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

摘要

基孔肯雅病毒 (CHIKV) 属于甲型病毒，它在人类中的感染会引起发烧，称为基孔肯雅热 (CHIKF)。这是一种突然发烧，可能对人类造成严重影响。传播给人类的方式是由于蚊子的叮咬而发生的。迄今为止，全世界有成千上万的人受到这种病毒的影响。迄今为止，市场上还没有有希望的药物或疫苗来治愈这种病毒感染。因此，需要针对 CHIKV 的 nsp3 的有希望的候选者。在目前的工作中，基于多组分反应中获得的产物设计了一个化合物库。然后，基于对使用分子对接获得的 CHIKV 的 nsp3 的结合能过滤设计的化合物。进一步，( MD) 在不同温度下进行模拟，即 300、325、350、375 和 400 K。通过从 MD 模拟获得的不同轨迹研究复合物的结合或形成。结合能的准确信息是通过执行 MM-GBSA 计算确定的，并且在 300 K 时观察到最佳抑制，因为形成复合物的自由能变化为 –7.0523 kcal/mol。

由 Ramaswamy H. Sarma 传达