Yang Jiaan, Zhang Peng, Cheng Wen Xiang, Lu Youyong, Gang Wu, Ren Gang
Chinese Academy of Sciences.
Peking University Cancer Hospital & Institute.
Res Sq. 2021 Sep 13:rs.3.rs-800496. doi: 10.21203/rs.3.rs-800496/v1.
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 advances in protein structure fingerprint technology to study the folding conformational changes induced by mutations. With the integration of both protein sequences and folding conformations and alignments of SARS-CoV to SARS-CoV-2, the UK variant and India variant, we found that structural variations in the spike protein at the binding interface interacting with ACE2 play a critical role in coronavirus entry into human cells. Additionally, the 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.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的突变会影响病毒功能，因为氨基酸残基的替换会同时影响其物理化学性质和折叠构象。尽管已有大量关于SARS-CoV-2的数据，但由于缺乏有效的结构分析，关于病毒功能如何因突变而变化的研究受到了阻碍。在此，我们利用蛋白质结构指纹技术的进展来研究由突变引起的折叠构象变化。通过整合蛋白质序列、折叠构象以及将严重急性呼吸综合征冠状病毒（SARS-CoV）与SARS-CoV-2、英国变种和印度变种进行比对，我们发现刺突蛋白与血管紧张素转换酶2（ACE2）相互作用的结合界面处的结构变异在冠状病毒进入人体细胞过程中起关键作用。此外，在SARS-CoV-2的进化过程中，这些结构变异会影响疫苗效力和药物功能。对结构变异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变种是如何在全球范围内导致更严重的急性疾病的。
