Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Laboratory of Veterinary Epidemiology and Microbiology LR16IPT03, Institut Pasteur of Tunis. University of Tunis El Manar, Tunis, Tunisia.
Biochem Biophys Res Commun. 2020 Jun 30;527(3):702-708. doi: 10.1016/j.bbrc.2020.05.028. Epub 2020 May 14.
The spread of COVID-19 caused by the SARS-CoV-2 outbreak has been growing since its first identification in December 2019. The publishing of the first SARS-CoV-2 genome made a valuable source of data to study the details about its phylogeny, evolution, and interaction with the host. Protein-protein binding assays have confirmed that Angiotensin-converting enzyme 2 (ACE2) is more likely to be the cell receptor through which the virus invades the host cell. In the present work, we provide an insight into the interaction of the viral spike Receptor Binding Domain (RBD) from different coronavirus isolates with host ACE2 protein. By calculating the binding energy score between RBD and ACE2, we highlighted the putative jump in the affinity from a progenitor form of SARS-CoV-2 to the current virus responsible for COVID-19 outbreak. Our result was consistent with previously reported phylogenetic analysis and corroborates the opinion that the interface segment of the spike protein RBD might be acquired by SARS-CoV-2 via a complex evolutionary process rather than a progressive accumulation of mutations. We also highlighted the relevance of Q493 and P499 amino acid residues of SARS-CoV-2 RBD for binding to human ACE2 and maintaining the stability of the interface. Moreover, we show from the structural analysis that it is unlikely for the interface residues to be the result of genetic engineering. Finally, we studied the impact of eight different variants located at the interaction surface of ACE2, on the complex formation with SARS-CoV-2 RBD. We found that none of them is likely to disrupt the interaction with the viral RBD of SARS-CoV-2.
自 2019 年 12 月首次发现 SARS-CoV-2 引发的 COVID-19 疫情以来，其传播一直在加剧。SARS-CoV-2 基因组的首次发布为研究其系统发育、进化和与宿主相互作用的细节提供了宝贵的数据来源。蛋白-蛋白结合测定已经证实血管紧张素转换酶 2（ACE2）更有可能是病毒入侵宿主细胞的细胞受体。在本工作中，我们深入研究了来自不同冠状病毒分离株的病毒刺突受体结合域（RBD）与宿主 ACE2 蛋白的相互作用。通过计算 RBD 和 ACE2 之间的结合能评分，我们突出了从 SARS-CoV-2 的前体形式到目前导致 COVID-19 爆发的病毒的亲和力的潜在跳跃。我们的结果与先前报道的系统发育分析一致，并证实了刺突蛋白 RBD 的界面片段可能通过复杂的进化过程而不是 SARS-CoV-2 突变的累积获得的观点。我们还强调了 SARS-CoV-2 RBD 的 Q493 和 P499 氨基酸残基对与人 ACE2 结合和维持界面稳定性的相关性。此外，我们从结构分析中表明，界面残基不太可能是基因工程的结果。最后，我们研究了位于 ACE2 相互作用表面的八个不同变体对与 SARS-CoV-2 RBD 形成复合物的影响。我们发现它们都不太可能破坏与 SARS-CoV-2 的病毒 RBD 的相互作用。
