SARS-CoV-2穗蛋白/血管紧张素转化酶2复合物的计算丙氨酸扫描和结构分析。,ACS Nano

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SARS-CoV-2穗蛋白/血管紧张素转化酶2复合物的计算丙氨酸扫描和结构分析。
ACS Nano ( IF 15.8 ) Pub Date : 2020-08-24 , DOI: 10.1021/acsnano.0c04674
Erik Laurini ₁ , Domenico Marson ₁ , Suzana Aulic ₁ , Maurizio Fermeglia ₁ , Sabrina Pricl _{1,

2}

Affiliation

最近出现的病原体严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是2019年冠状病毒病的病原体（COVID-19），正在引起全球性流行病，对全球公共卫生和经济构成巨大挑战。SARS-CoV-2宿主细胞的进入是由病毒跨膜棘突糖蛋白（S蛋白）与血管紧张素转化酶2基因（ACE2）相互作用而介导的，血管紧张素转化酶2基因是肾素-血管紧张素激素系统的一种重要的反调节羧肽酶，是调节血容量，全身血管阻力和心血管稳态的关键调节器。因此，这项工作报告了基于原子的，可靠的计算机技术SARS-CoV-2 S蛋白的受体结合域与其宿主细胞受体ACE2之间相互作用的结构和能量框架，可对病毒/受体识别中的主要分子决定因素进行定性和定量分析。特别是，ACE2上的残基D38，K31，E37，K353和Y41以及SARS-CoV-2 S蛋白受体结合域上的Q498，T500和R403被确定为真正的热点，有助于形成和确定相关蛋白质-蛋白质界面的稳定性。总体而言，这些结果可用于估算病毒蛋白与在COVID-19患者中发现的ACE2受体的不同等位基因变体的结合亲和力，并用于基于结构的有效设计和开发中和抗体，疫苗，

"点击查看英文标题和摘要"

Computational Alanine Scanning and Structural Analysis of the SARS-CoV-2 Spike Protein/Angiotensin-Converting Enzyme 2 Complex.

The recent emergence of the pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent for the coronavirus disease 2019 (COVID-19), is causing a global pandemic that poses enormous challenges to global public health and economies. SARS-CoV-2 host cell entry is mediated by the interaction of the viral transmembrane spike glycoprotein (S-protein) with the angiotensin-converting enzyme 2 gene (ACE2), an essential counter-regulatory carboxypeptidase of the renin-angiotensin hormone system that is a critical regulator of blood volume, systemic vascular resistance, and thus cardiovascular homeostasis. Accordingly, this work reports an atomistic-based, reliable in silico structural and energetic framework of the interactions between the receptor-binding domain of the SARS-CoV-2 S-protein and its host cellular receptor ACE2 that provides qualitative and quantitative insights into the main molecular determinants in virus/receptor recognition. In particular, residues D38, K31, E37, K353, and Y41 on ACE2 and Q498, T500, and R403 on the SARS-CoV-2 S-protein receptor-binding domain are determined as true hot spots, contributing to shaping and determining the stability of the relevant protein–protein interface. Overall, these results could be used to estimate the binding affinity of the viral protein to different allelic variants of ACE2 receptors discovered in COVID-19 patients and for the effective structure-based design and development of neutralizing antibodies, vaccines, and protein/protein inhibitors against this terrible new coronavirus.

更新日期：2020-09-22

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