Department of Chemistry, Atma Ram Sanatan Dharma College, University of Delhi, Delhi, India.
Department of Chemistry, Shivaji College, University of Delhi, Delhi, India.
J Biomol Struct Dyn. 2022 Aug;40(13):5827-5835. doi: 10.1080/07391102.2021.1873863. Epub 2021 Jan 21.
Infection due to the Chikungunya virus (CHIKV) has taken the life of lots of people; and researchers are working to find the vaccine or promisng drug candidates against this viral infection. In this work, the authors have designed one component reaction based on the thia-/oxa-azolidineone and created a library of 2000 molecules based on the product obtained. Further, the compounds were screened through the docking using iGemdock against the non-structural protein 2 (nsp2) of CHIKV. Molecular docking gives the binding energy (BE) or energy for the formation of the complex between the designed compound and nsp2 of CHIKV; and CMPD222 gave the lowest energy. This is based on the energy obtained from van der Waal's interaction, hydrogen bonding and electrostatic instructions. Further, molecular dynamics simulations (MDS) of nsp2 of CHIKV with and without screened compound (222) were performed to validate the docking results and the change in free energy for the formation of the complex is -10.8327 kcal/mol. To explore the potential of CMPD222, the MDS of the CMPD222-nsp2 of CHIKV were performed at different temperatures (325, 350, 375 and 400 K) to understand the inhibition of the protease. MM-GBSA calculations were performed to determined change in entropy, change in enthalpy and change in free energy to understand the inhibition. Maximum inhibition of nsp2 of CHIKV with CMPD222 is observed at 375 K with a change in free energy of -19.3754 kcal/mol.Communicated by Ramaswamy H. Sarma.
基孔肯雅病毒（CHIKV）感染导致许多人死亡；研究人员正在努力寻找针对这种病毒感染的疫苗或有前途的药物候选物。在这项工作中，作者基于噻唑烷酮/噁唑烷酮设计了一个单组分反应，并基于得到的产物创建了 2000 个分子的库。此外，通过使用 iGemdock 对 CHIKV 的非结构蛋白 2（nsp2）进行对接筛选化合物。分子对接给出了设计化合物与 CHIKV 的 nsp2 形成复合物的结合能（BE）或能量；CMPD222 给出了最低的能量。这是基于范德华相互作用、氢键和静电指令获得的能量。此外，还对 CHIKV 的 nsp2 进行了有和没有筛选化合物（222）的分子动力学模拟（MDS），以验证对接结果和形成复合物的自由能变化为-10.8327 kcal/mol。为了探索 CMPD222 的潜力，在不同温度（325、350、375 和 400 K）下对 CMPD222-CHIKV nsp2 进行了 MDS，以了解蛋白酶的抑制作用。进行 MM-GBSA 计算以确定熵变、焓变和自由能变化，以了解抑制作用。在 375 K 时，CMPD222 对 CHIKV nsp2 的最大抑制作用观察到自由能变化为-19.3754 kcal/mol。由 Ramaswamy H. Sarma 传达。
