Ilyas Mubashar, Muhammad Shabbir, Iqbal Javed, Amin Saniyah, Al-Sehemi Abdullah G, Algarni H, Alarfaji Saleh S, Alshahrani Mohammad Y, Ayub Khurshid
Department of Chemistry, University of Agriculture, Faisalabad, 38000 Pakistan.
Department of Chemistry, College of Science, King Khalid University, P.O. Box 9004, Abha, 61413 Saudi Arabia.
Chem Zvesti. 2022;76(10):6271-6285. doi: 10.1007/s11696-022-02298-7. Epub 2022 Jun 22.
The world is now facing intolerable damage in all sectors of life because of the deadly COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2. The discovery and development of anti-SARS-CoV-2 drugs have become pragmatic in the time needed to fight against this pandemic. The non-structural protein 3 is essential for the replication of transcriptase complex (RTC) and may be regarded as a possible target against SARS-CoV-2. Here, we have used a comprehensive in silico technique to find potent drug molecules against the NSP3 receptor of SARS-CoV-2. Virtual screening of 150 Isatin derivatives taken from PubChem was performed based on their binding affinity estimated by docking simulations, resulting in the selection of 46 ligands having binding energy greater than -7.1 kcal/mol. Moreover, the molecular interactions of the nine best-docked ligands having a binding energy of ≥ -8.5 kcal/mol were analyzed. The molecular interactions showed that the three ligands (S5, S16, and S42) were stabilized by forming hydrogen bonds and other significant interactions. Molecular dynamic simulations were performed to mimic an in vitro protein-like aqueous environment and to check the stability of the best three ligands and NSP3 complexes in an aqueous environment. The binding energy of the S5, S16, and S42 systems obtained from the molecular mechanics Poisson-Boltzmann surface area also favor the system's stability. The MD and MM/PBSA results explore that S5, S16, and S42 are more stable and can be considered more potent drug candidates against COVID-19 disease.
The online version contains supplementary material available at 10.1007/s11696-022-02298-7.
由于严重急性呼吸综合征冠状病毒2引发的致命性新冠疫情，世界目前在生活的各个领域都面临着无法忍受的损害。在对抗这场疫情所需的时间内，抗SARS-CoV-2药物的发现和开发已变得切实可行。非结构蛋白3对于转录酶复合物（RTC）的复制至关重要，可被视为对抗SARS-CoV-2的一个可能靶点。在此，我们使用了一种全面的计算机模拟技术来寻找针对SARS-CoV-2的NSP3受体的有效药物分子。基于通过对接模拟估计的结合亲和力，对从PubChem获取的150种异吲哚酮衍生物进行了虚拟筛选，结果选出了46种结合能大于-7.1千卡/摩尔的配体。此外，分析了结合能≥ -8.5千卡/摩尔的9种最佳对接配体的分子相互作用。分子相互作用表明，三种配体（S5、S16和S42）通过形成氢键和其他重要相互作用而稳定。进行了分子动力学模拟以模拟体外类似蛋白质的水环境，并检查最佳的三种配体与NSP3复合物在水环境中的稳定性。从分子力学泊松-玻尔兹曼表面积获得的S5、S16和S42系统的结合能也有利于系统的稳定性。分子动力学和分子力学/泊松-玻尔兹曼表面积计算结果表明，S5、S16和S42更稳定，可被视为对抗新冠疾病更有效的候选药物。
在线版本包含可在10.1007/s11696-022-02298-7获取的补充材料。
