Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
The Alexander Grass Center for Bioengineering, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Viruses. 2020 Apr 30;12(5):497. doi: 10.3390/v12050497.
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.
COVID-19 疾病已困扰全球 200 多个国家，感染病例超过 300 万例，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 ACE2 受体与 SARS-CoV-2 刺突蛋白之间的相互作用与其他致病性冠状病毒之间的相互作用。SARS-CoV、SARS-CoV-2 和 HCoV-NL63 均将 ACE2 识别为天然受体，但与 ACE2 具有不同的结合界面和不同的残基残基相互作用网络。SARS-CoV 和 SARS-CoV-2 通过平衡能量和动力学达到相当的结合亲和力。SARS-CoV-2-ACE2 复合物与 SARS-CoV-ACE2 复合物相比，包含更多的接触点、更大的界面面积和更小的界面残基波动。这些发现揭示了冠状病毒在宿主识别方面的独特进化探索。我们推测，细胞受体结合策略的多功能性对治疗策略具有直接影响。
