The SARS-CoV-2 Exerts a Distinctive Strategy for Interacting with the ACE2 Human Receptor
The SARS-CoV-2 Exerts a Distinctive Strategy for Interacting with the ACE2 Human Receptor
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DOI：
10.3390/v12050497
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发表时间：
2020-05-01
期刊：
影响因子：
4.7
通讯作者：
Linial, Michal
中科院分区：
文献类型：
--
作者：
Brielle, Esther S.;Schneidman-Duhovny, Dina;Linial, Michal
COVID-19疾病已困扰200多个国家，超过300万例病例，并在3个月内导致超过20万人死亡。为了深入了解SARS-CoV-2病毒的高感染率，我们使用分子动力学模拟比较了人类ACE 2受体和SARS-CoV-2刺突蛋白与其他致病性冠状病毒之间的相互作用。SARS-CoV、SARS-CoV-2和HCoV-NL 63识别ACE 2作为天然受体，但与ACE 2呈现不同的结合界面和不同的残基-残基接触网络。SARS-CoV和SARS-CoV-2通过平衡能量学和动力学而具有可比的结合亲和力。相对于SARS-CoV-ACE 2复合物，SARS-CoV-2-ACE 2复合物含有更多的接触，更大的界面面积和减少的界面残基波动。这些发现揭示了冠状病毒对宿主识别的特殊进化探索。我们假设，细胞受体结合策略的多功能性对治疗策略有直接的影响。
The COVID-19 disease has plagued over 200 countries with over three million cases and has resulted in over 200,000 deaths within 3 months. To gain insight into the high infection rate of the SARS-CoV-2 virus, we compare the interaction between the human ACE2 receptor and the SARS-CoV-2 spike protein with that of other pathogenic coronaviruses using molecular dynamics simulations. SARS-CoV, SARS-CoV-2, and HCoV-NL63 recognize ACE2 as the natural receptor but present a distinct binding interface to ACE2 and a different network of residue-residue contacts. SARS-CoV and SARS-CoV-2 have comparable binding affinities achieved by balancing energetics and dynamics. The SARS-CoV-2-ACE2 complex contains a higher number of contacts, a larger interface area, and decreased interface residue fluctuations relative to the SARS-CoV-ACE2 complex. These findings expose an exceptional evolutionary exploration exerted by coronaviruses toward host recognition. We postulate that the versatility of cell receptor binding strategies has immediate implications for therapeutic strategies.