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Exploring the Spike-hACE 2 Residue–Residue Interaction in Human Coronaviruses SARS-CoV-2, SARS-CoV, and HCoV-NL63
Journal of Chemical Information and Modeling ( IF 5.6 ) Pub Date : 2022-05-26 , DOI: 10.1021/acs.jcim.1c01544
José X Lima Neto 1 , Davi S Vieira 2 , Jones de Andrade 3 , Umberto Laino Fulco 1
Affiliation  

Coronaviruses (CoVs) have been responsible for three major outbreaks since the beginning of the 21st century, and the emergence of the recent COVID-19 pandemic has resulted in considerable efforts to design new therapies against coronaviruses. Thus, it is crucial to understand the structural features of their major proteins related to the virus–host interaction. Several studies have shown that from the seven known CoV human pathogens, three of them use the human Angiotensin-Converting Enzyme 2 (hACE-2) to mediate their host’s cell entry: SARS-CoV-2, SARS-CoV, and HCoV-NL63. Therefore, we employed quantum biochemistry techniques within the density function theory (DFT) framework and the molecular fragmentation with conjugate caps (MFCC) approach to analyze the interactions between the hACE-2 and the spike protein-RBD of the three CoVs in order to map the hot-spot residues that form the recognition surface for these complexes and define the similarities and differences in the interaction scenario. The total interaction energy evaluated showed a good agreement with the experimental binding affinity order: SARS-2 > SARS > NL63. A detailed investigation revealed the energetically most relevant regions of hACE-2 and the spike protein for each complex, as well as the key residue–residue interactions. Our results provide valuable information to deeply understand the structural behavior and binding site characteristics that could help to develop antiviral therapeutics that inhibit protein–protein interactions between CoVs S protein and hACE-2.

中文翻译:

探索人类冠状病毒 SARS-CoV-2、SARS-CoV 和 HCoV-NL63 中的 Spike-hACE 2 残基-残基相互作用

自 21 世纪初以来,冠状病毒 (CoV) 已导致三场重大疫情暴发,最近新冠肺炎 (COVID-19) 大流行的出现促使人们为设计针对冠状病毒的新疗法付出了巨大的努力。因此,了解与病毒-宿主相互作用相关的主要蛋白质的结构特征至关重要。多项研究表明,在七种已知的人类冠状病毒病原体中,其中三种利用人类血管紧张素转换酶 2 (hACE-2) 介导宿主细胞进入:SARS-CoV-2、SARS-CoV 和 HCoV-NL63 。因此,我们采用密度函数理论(DFT)框架内的量子生物化学技术和结合帽分子片段化(MFCC)方法来分析hACE-2和三种冠状病毒的刺突蛋白-RBD之间的相互作用,以绘制图谱形成这些复合物识别表面并定义相互作用场景中的相似点和差异的热点残基。评估的总相互作用能与实验结合亲和力顺序非常一致:SARS-2 > SARS > NL63。详细的研究揭示了 hACE-2 和每个复合物的刺突蛋白在能量上最相关的区域,以及关键的残基-残基相互作用。我们的结果为深入了解结构行为和结合位点特征提供了有价值的信息,这有助于开发抑制 CoV S 蛋白和 hACE-2 之间蛋白质-蛋白质相互作用的抗病毒疗法。
更新日期:2022-05-26
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