Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, Guangdong, China.
Micro Biotech, Ltd., Shanghai, 200123, China.
Sci Rep. 2021 Nov 11;11(1):22042. doi: 10.1038/s41598-021-01650-3.
The mutation of SARS-CoV-2 influences viral function as residue replacements affect both physiochemical properties and folding conformations. Although a large amount of data on SARS-CoV-2 is available, the investigation of how viral functions change in response to mutations is hampered by a lack of effective structural analysis. Here, we exploit the advances of protein structure fingerprint technology to study the folding conformational changes induced by mutations. With integration of both protein sequences and folding conformations, the structures are aligned for SARS-CoV to SARS-CoV-2, including Alpha variant (lineage B.1.1.7) and Delta variant (lineage B.1.617.2). The results showed that the virus evolution with change in mutational positions and physicochemical properties increased the affinity between spike protein and ACE2, which plays a critical role in coronavirus entry into human cells. Additionally, these structural variations impact vaccine effectiveness and drug function over the course of SARS-CoV-2 evolution. The analysis of structural variations revealed how the coronavirus has gradually evolved in both structure and function and how the SARS-CoV-2 variants have contributed to more severe acute disease worldwide.
SARS-CoV-2 的突变影响病毒功能，因为残基替换会影响理化性质和折叠构象。尽管已经有大量关于 SARS-CoV-2 的数据，但由于缺乏有效的结构分析，研究病毒功能如何响应突变的工作受到了阻碍。在这里，我们利用蛋白质结构指纹技术的进展来研究突变引起的折叠构象变化。通过整合蛋白质序列和折叠构象，对 SARS-CoV 到 SARS-CoV-2 的结构进行对齐，包括 Alpha 变体（谱系 B.1.1.7）和 Delta 变体（谱系 B.1.617.2）。结果表明，病毒进化中突变位置和理化性质的变化增加了刺突蛋白与 ACE2 的亲和力，ACE2 在冠状病毒进入人体细胞中起着关键作用。此外，这些结构变化会影响 SARS-CoV-2 进化过程中的疫苗效力和药物功能。结构变化的分析揭示了冠状病毒在结构和功能上是如何逐渐进化的，以及 SARS-CoV-2 变体如何导致全球更严重的急性疾病。
