PDF(Sci-hub)
Abstract：
Spike protein (S protein) is the virus \"key\" to infect cells and is able to strongly bind to the human angiotensin-converting enzyme2 (ACE2), as has been reported. In fact, Spike structure and function is known to be highly important for cell infection as well as for entering the brain. Growing evidence indicates that different types of coronaviruses not only affect the respiratory system, but they might also invade the central nervous system (CNS). However, very little evidence has been so far reported on the presence of COVID-19 in the brain, and the potential exploitation, by this virus, of the lung to brain axis to reach neurons has not been completely understood. In this Article, we assessed the SARS-CoV and SARS-CoV-2 Spike protein sequence, structure, and electrostatic potential using computational approaches. Our results showed that the S proteins of SARS-CoV-2 and SARS-CoV are highly similar, sharing a sequence identity of 77%. In addition, we found that the SARS-CoV-2 S protein is slightly more positively charged than that of SARS-CoV since it contains four more positively charged residues and five less negatively charged residues which may lead to an increased affinity to bind to negatively charged regions of other molecules through nonspecific and specific interactions. Analysis the S protein binding to the host ACE2 receptor showed a 30% higher binding energy for SARS-CoV-2 than for the SARS-CoV S protein. These results might be useful for understanding the mechanism of cell entry, blood-brain barrier crossing, and clinical features related to the CNS infection by SARS-CoV-2.
摘要：
刺突蛋白（S蛋白）是感染细胞的病毒“关键”，能够与人血管紧张素转换酶2（ACE2）强结合，据报道。事实上,已知尖峰结构和功能对于细胞感染以及进入大脑非常重要。越来越多的证据表明，不同类型的冠状病毒不仅影响呼吸系统，但它们也可能侵入中枢神经系统（CNS）。然而,到目前为止，关于大脑中存在COVID-19的证据很少，以及潜在的剥削，这种病毒，肺到脑轴到达神经元的情况尚未完全了解。在这篇文章中，我们评估了SARS-CoV和SARS-CoV-2尖峰蛋白序列，结构,和静电势使用计算方法。我们的结果表明，SARS-CoV-2和SARS-CoV的S蛋白高度相似，共享77%的序列同一性。此外,我们发现，SARS-CoV-2S蛋白的带正电荷比SARS-CoV略高，因为它包含四个带正电荷的残基和五个带负电荷的残基，这可能导致与带负电荷的区域结合的亲和力增加。其他分子通过非特异性和特异性相互作用。分析S蛋白与宿主ACE2受体的结合显示，SARS-CoV-2的结合能比SARS-CoVS蛋白高30％。这些结果可能有助于理解细胞进入的机制，血脑屏障穿越,和与SARS-CoV-2感染中枢神经系统相关的临床特征。
