Jahromi Ahmad Miri, Solhjoo Aida, Ghasemi Mehdi, Khedri Mohammad, Maleki Reza, Tayebi Lobat
Computational Biology and Chemistry Group (CBCG), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
Mater Chem Phys. 2022 Jan 15;276:125382. doi: 10.1016/j.matchemphys.2021.125382. Epub 2021 Oct 28.
The recent pandemic of COVID-19 has raised global health concerns. Preventing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) activity in the body is a very promising method to overcome the COVID-19 pandemic. One of the prevention methods is constraining the binding process among the human cell receptor-ACE2 and coronavirus spike protein. In the research done, the effect of deformation of the spike protein structure, due to the covalent organic frameworks (COFs), in reducing the interactions of ACE2 and the spike protein by the computational method was investigated. In this regard, atomic analysis of the interactions of ACE2 and the spike protein is provided using a molecular dynamics simulation. First, we investigated the interactions of the three different COFs, including COF-78, DAAQ-TFP, and COF-OEt, with the spike protein by analyzing the bond energies, as well as structural changes of the spike protein. Then, intermolecular interactions of the deformed spike protein along with ACE2 were assessed to clarify the protein's fusion after the deformation. As indicated by the results, although all introduced COFs deformed the spike protein in an effective way, COF-78 showed the best performance in the prevention of spike protein-ACE2 interactions by changing the molecular structure of the protein. Indeed, the interaction analysis of the deformed spike protein by COF-78 with the ACE2 showed that their interactions had the lowest absolute value of energy, along with the least amount of hydrogen bonds, in which the compaction of the protein was lower compared to the other deformed proteins. Moreover, having a high contact area with an aqueous media as well as severe fluctuations during the simulation time confirmed the positive performance of COF-78. In the current study, we aimed to introduce novel materials and COVID-19 prevention methodology that can be used in face masks and for surface disinfection.
近期的新冠疫情引发了全球对健康的关注。预防严重急性呼吸综合征冠状病毒2（SARS-CoV-2）在体内的活动是克服新冠疫情的一种非常有前景的方法。预防方法之一是限制人类细胞受体血管紧张素转换酶2（ACE2）与冠状病毒刺突蛋白之间的结合过程。在已开展的研究中，通过计算方法研究了共价有机框架（COFs）导致的刺突蛋白结构变形对减少ACE2与刺突蛋白相互作用的影响。在这方面，使用分子动力学模拟对ACE2与刺突蛋白的相互作用进行了原子分析。首先，我们通过分析键能以及刺突蛋白的结构变化，研究了三种不同的COFs（包括COF-78、DAAQ-TFP和COF-OEt）与刺突蛋白的相互作用。然后，评估了变形后的刺突蛋白与ACE2之间的分子间相互作用，以阐明变形后蛋白质的融合情况。结果表明，尽管所有引入的COFs都有效地使刺突蛋白发生了变形，但COF-78通过改变蛋白质的分子结构，在预防刺突蛋白与ACE2相互作用方面表现出最佳性能。实际上，COF-78使刺突蛋白变形后与ACE2的相互作用分析表明，它们的相互作用能量绝对值最低，氢键数量也最少，与其他变形蛋白相比，该蛋白质的紧密程度更低。此外，在模拟时间内与水性介质有高接触面积以及剧烈波动，证实了COF-78的良好性能。在当前研究中，我们旨在引入可用于口罩和表面消毒的新型材料及新冠预防方法。
