Conversion rate to the secondary conformation state in the binding mode of SARS-CoV-2 spike protein to human ACE2 may predict infectivity efficacy of the underlying virus mutant
biorxiv(2021)
摘要
Since its outbreak in 2019 SARS-CoV-2 has spread with high transmission efficiency across the world, putting health care as well as economic systems under pressure [[1][1], [2][2]]. During the course of the pandemic, the originally identified SARS-CoV-2 variant has been widely replaced by various mutant versions, which showed enhanced fitness due to increased infection and transmission rates [[3][3], [4][4]]. In order to find an explanation, why SARS-CoV-2 and its emerging mutated versions showed enhanced transfection efficiency as compared to SARS-CoV 2002, an improved binding affinity of the spike protein to human ACE has been proposed by crystal structure analysis and was identified in cell culture models [[5][5]-[7][6]]. Kinetic analysis of the interaction of various spike protein constructs with the human ACE2 was considered to be best described by a Langmuir based 1:1 stoichiometric interaction. However, we demonstrate in this report that the SARS-CoV-2 spike protein interaction with ACE2 is best described by a two-step interaction, which is defined by an initial binding event followed by a slower secondary rate transition that enhances the stability of the complex by a factor of ∼190 with an overall KD of 0.20 nM. In addition, we show that the secondary rate transition is not only present in SARS-CoV-2 wt but is also found in B.1.1.7 where its transition rate is five-fold increased.
### Competing Interest Statement
The authors have declared no competing interest.
[1]: #ref-1
[2]: #ref-2
[3]: #ref-3
[4]: #ref-4
[5]: #ref-5
[6]: #ref-7
更多查看译文
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要