Mahnam Karim, Rajaee Seyed Mehdi
Department of Biology, Faculty of Sciences, Shahrekord University, Shahrekord, Iran.
Nanotechnology Research Center, Shahrekord University, Shahrekord, Iran.
J Biomol Struct Dyn. 2023;41(23):14540-14565. doi: 10.1080/07391102.2023.2183033. Epub 2023 Mar 28.
The spike protein of coronavirus is crucial in binding and arrival of the virus to the human cell via binding to the human ACE2 receptor. In this study, at first 25 antiviral phytochemicals were docked into the RBD domain of spike protein, and then all complexes and free RBD domains were separately subjected to molecular dynamics simulation for 100 ns and MM/PBSA binding free energy calculation. In this phase, four ligands were chosen as hit compounds and a natural compound database (NPASS) was screened based on high similarity with these ligands, and 367 ligands were found. Then the same previous procedure was repeated for these ligands and ADME properties were investigated. Finally, virtual screening and 4400 ns MD simulation and MM/PBSA calculation revealed that new ligands including NPC67959, NPC157855, NPC248793, and NPC216361 can inhibit the RBD domain of spike protein and we propose them as potential drugs for experimental studies.Communicated by Ramaswamy H. Sarma.
冠状病毒的刺突蛋白对于病毒通过与人类ACE2受体结合而与人类细胞结合并进入细胞至关重要。在本研究中，首先将25种抗病毒植物化学物质对接至刺突蛋白的RBD结构域，然后将所有复合物和游离的RBD结构域分别进行100 ns的分子动力学模拟和MM/PBSA结合自由能计算。在此阶段，选择了四种配体作为命中化合物，并基于与这些配体的高度相似性筛选了一个天然化合物数据库（NPASS），共发现367种配体。然后对这些配体重复上述相同步骤，并研究其ADME性质。最后，虚拟筛选以及4400 ns的分子动力学模拟和MM/PBSA计算表明，包括NPC67959、NPC157855、NPC248793和NPC216361在内的新配体可以抑制刺突蛋白的RBD结构域，我们建议将它们作为实验研究的潜在药物。由Ramaswamy H. Sarma传达。
