Faisal H M Nasrullah, Katti Kalpana S, Katti Dinesh R
Department of Civil, Construction and Environmental Engineering, North Dakota State University, Fargo, ND 58108, United States.
Center for Engineered Cancer Testbeds, North Dakota State University, Fargo, ND 58108, United States.
Chem Phys. 2021 Nov 1;551:111353. doi: 10.1016/j.chemphys.2021.111353. Epub 2021 Sep 6.
The SARS-CoV-2 coronavirus (COVID-19) that is causing the massive global pandemic exhibits similar human cell invasion mechanism as the coronavirus SARS-CoV, which had significantly lower fatalities. The cell membrane protein Angiotensin-converting enzyme 2 (ACE2) is the initiation point for both the coronavirus infections in humans. Here, we model the molecular interactions and mechanical properties of ACE2 with both SARS-CoV and COVID-19 spike protein receptor-binding domains (RBD). We report that the COVID-19 spike RBD interacts with ACE2 more strongly and at only two protein residues, as compared to multi-residue interaction of the SARS-CoV. Although both coronaviruses stiffen the ACE2, the impact of COVID-19 is six times larger, which points towards differences in the severity of the reported respiratory distress. The recognition of specific residues of ACE2 attachments to coronaviruses is important as the residues suggest potential sites of intervention to inhibit attachment and subsequent entry of the COVID-19 into human host cells.
引发全球大规模疫情的严重急性呼吸综合征冠状病毒2（SARS-CoV-2，即新冠病毒）展现出了与致死率低得多的冠状病毒SARS-CoV相似的入侵人体细胞机制。细胞膜蛋白血管紧张素转换酶2（ACE2）是这两种冠状病毒感染人类的起始点。在此，我们对ACE2与SARS-CoV和新冠病毒刺突蛋白受体结合域（RBD）的分子相互作用及力学性质进行建模。我们报告称，与SARS-CoV的多残基相互作用相比，新冠病毒刺突RBD与ACE2的相互作用更强，且仅涉及两个蛋白质残基。尽管两种冠状病毒都会使ACE2变硬，但新冠病毒的影响要大六倍，这表明了所报告的呼吸窘迫严重程度存在差异。识别ACE2与冠状病毒结合的特定残基很重要，因为这些残基提示了抑制新冠病毒附着及随后进入人类宿主细胞的潜在干预位点。
