Louvain Institute of Biomolecular Science and Technology, Université catholique de Louvain, Louvain-la-Neuve, Belgium.
Institute of Fundamental Technological Research, Polish Academy of Sciences, Pawińskiego 5B, 02-106, Warsaw, Poland.
Nat Commun. 2021 Nov 30;12(1):6977. doi: 10.1038/s41467-021-27325-1.
Despite an unprecedented global gain in knowledge since the emergence of SARS-CoV-2, almost all mechanistic knowledge related to the molecular and cellular details of viral replication, pathology and virulence has been generated using early prototypic isolates of SARS-CoV-2. Here, using atomic force microscopy and molecular dynamics, we investigated how these mutations quantitatively affected the kinetic, thermodynamic and structural properties of RBD-ACE2 complex formation. We observed for several variants of concern a significant increase in the RBD-ACE2 complex stability. While the N501Y and E484Q mutations are particularly important for the greater stability, the N501Y mutation is unlikely to significantly affect antibody neutralization. This work provides unprecedented atomistic detail on the binding of SARS-CoV-2 variants and provides insight into the impact of viral mutations on infection-induced immunity.
尽管自 SARS-CoV-2 出现以来，全球在知识方面取得了前所未有的进步，但几乎所有与病毒复制、病理学和毒力的分子和细胞细节相关的机制知识都是使用 SARS-CoV-2 的早期原型分离株生成的。在这里，我们使用原子力显微镜和分子动力学研究了这些突变如何定量影响 RBD-ACE2 复合物形成的动力学、热力学和结构特性。我们观察到几种关注的变体的 RBD-ACE2 复合物稳定性显著增加。虽然 N501Y 和 E484Q 突变对更高的稳定性特别重要，但 N501Y 突变不太可能显著影响抗体中和作用。这项工作提供了 SARS-CoV-2 变体结合的空前原子细节，并深入了解病毒突变对感染诱导免疫的影响。
