Background

The emergence of a novel coronavirus (SARS-CoV-2) has been spreading worldwide in 2020. Coronaviruses could mainly cause respiratory tract infections in humans and multiple system infections in many animals. The coronavirus enters the host cell through the binding of surface spike glycoprotein (S Protein) with host angiotensin-converting enzyme-Ⅱ (ACE2) protein.

Methods

ACE2 sequences of various species were aligned with human ACE2, accordingly, homology models for different species were constructed. Then, S-protein-ACE2 complexes were constructed using the generated homology models. The molecular dynamics simulations and Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) were carried out to study the dynamical behavior of the generated S-ACE2 virtual complexes. Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF) and Radius of Gyration (Rg) were calculated to evaluate protein stability and compactness.

Results

The binding free energies of S protein with ACE2 from Procyon lotor and Camelus dromedarius are about equal to that of humans. By comparing the free binding energies it were possible to identify potential viral hosts that could transmit the virus to human (risk of cross-species transmission). The predication showed that, besides human beings, SARS-CoV-2 may possibly infect Procyon lotor and Camelus dromedarius as well.

中文翻译：

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病毒最喜欢哪个物种：SARS-CoV-2 S蛋白与ACE2受体的结合模式研究

背景

2020年，新型冠状病毒（SARS-CoV-2）的出现在全球范围内蔓延。冠状病毒主要引起人类呼吸道感染和许多动物的多系统感染。冠状病毒通过表面刺突糖蛋白（S蛋白）与宿主血管紧张素转换酶-Ⅱ（ACE2）蛋白结合进入宿主细胞。

方法

将各种物种的ACE2序列与人类ACE2进行比对，据此构建不同物种的同源模型。然后，使用生成的同源模型构建 S 蛋白-ACE2 复合物。进行分子动力学模拟和分子力学/泊松-玻尔兹曼表面积 (MM/PBSA) 以研究生成的 S-ACE2 虚拟复合物的动力学行为。计算均方根偏差 (RMSD)、均方根波动 (RMSF) 和回转半径 (Rg) 以评估蛋白质稳定性和紧密度。

结果

Procyon lotor和Camelus dromedarius的 S 蛋白与 ACE2 的结合自由能与人类大致相当。通过比较自由结合能，可以确定可能将病毒传播给人类的潜在病毒宿主（跨物种传播的风险）。预测表明，除了人类，SARS-CoV-2 还可能感染Procyon lotor和Camelus dromedarius。