Institute of Biophysics, School of Physics, Huazhong University of Science and Technology, Wuhan 430074, China.
Viruses. 2020 Apr 10;12(4):428. doi: 10.3390/v12040428.
The outbreak of a novel coronavirus, which was later formally named the severe acute respiratory coronavirus 2 (SARS-CoV-2), has caused a worldwide public health crisis. Previous studies showed that SARS-CoV-2 is highly homologous to SARS-CoV and infects humans through the binding of the spike protein to ACE2. Here, we have systematically studied the molecular mechanisms of human infection with SARS-CoV-2 and SARS-CoV by protein-protein docking and MD simulations. It was found that SARS-CoV-2 binds ACE2 with a higher affinity than SARS-CoV, which may partly explain that SARS-CoV-2 is much more infectious than SARS-CoV. In addition, the spike protein of SARS-CoV-2 has a significantly lower free energy than that of SARS-CoV, suggesting that SARS-CoV-2 is more stable and may survive a higher temperature than SARS-CoV. This provides insights into the evolution of SARS-CoV-2 because SARS-like coronaviruses have originated in bats. Our computation also suggested that the RBD-ACE2 binding for SARS-CoV-2 is much more temperature-sensitive than that for SARS-CoV. Thus, it is expected that SARS-CoV-2 would decrease its infection ability much faster than SARS-CoV when the temperature rises. These findings would be beneficial for the disease prevention and drug/vaccine development of SARS-CoV-2.
新型冠状病毒（随后正式命名为严重急性呼吸综合征冠状病毒 2，SARS-CoV-2）的爆发引发了全球公共卫生危机。先前的研究表明，SARS-CoV-2 与 SARS-CoV 高度同源，通过刺突蛋白与 ACE2 的结合感染人类。在这里，我们通过蛋白-蛋白对接和 MD 模拟系统地研究了人类感染 SARS-CoV-2 和 SARS-CoV 的分子机制。结果发现，SARS-CoV-2 与 ACE2 的结合亲和力高于 SARS-CoV，这可能部分解释了 SARS-CoV-2 的传染性比 SARS-CoV 更强。此外，SARS-CoV-2 的刺突蛋白的自由能明显低于 SARS-CoV，表明 SARS-CoV-2 更稳定，可能比 SARS-CoV 能在更高的温度下存活。这为 SARS-CoV-2 的进化提供了新的见解，因为类似 SARS 的冠状病毒起源于蝙蝠。我们的计算还表明，SARS-CoV-2 的 RBD-ACE2 结合对温度的敏感性远高于 SARS-CoV。因此，预计当温度升高时，SARS-CoV-2 的感染能力会比 SARS-CoV 下降得更快。这些发现将有助于 SARS-CoV-2 的疾病预防和药物/疫苗开发。
