Božič Anže, Podgornik Rudolf
Department of Theoretical Physics, Jožef Stefan Institute, Jamova 39, Ljubljana SI-1000, Slovenia.
School of Physical Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Shijingshan District, Beijing 100049, China.
Virus Evol. 2023 Jun 29;9(2):vead040. doi: 10.1093/ve/vead040. eCollection 2023.
The spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for target recognition, cellular entry, and endosomal escape of the virus. At the same time, it is the part of the virus that exhibits the greatest sequence variation across the many variants which have emerged during its evolution. Recent studies have indicated that with progressive lineage emergence, the positive charge on the spike protein has been increasing, with certain positively charged amino acids (AAs) improving the binding of the spike protein to cell receptors. We have performed a detailed analysis of dissociable AAs of more than 1400 different SARS-CoV-2 lineages, which confirms these observations while suggesting that this progression has reached a plateau with Omicron and its subvariants and that the positive charge is not increasing further. Analysis of the nucleocapsid protein shows no similar increase in positive charge with novel variants, which further indicates that positive charge of the spike protein is being evolutionarily selected for. Furthermore, comparison with the spike proteins of known coronaviruses shows that already the wild-type SARS-CoV-2 spike protein carries an unusually large amount of positively charged AAs when compared to most other betacoronaviruses. Our study sheds light on the evolutionary changes in the number of dissociable AAs on the spike protein of SARS-CoV-2, complementing existing studies and providing a stepping stone towards a better understanding of the relationship between the spike protein charge and viral infectivity and transmissibility.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的刺突蛋白负责病毒的靶标识别、细胞进入和内体逃逸。同时，它也是病毒中在其进化过程中出现的众多变体间表现出最大序列变异的部分。最近的研究表明，随着进化分支的不断出现，刺突蛋白上的正电荷一直在增加，某些带正电荷的氨基酸（AAs）增强了刺突蛋白与细胞受体的结合。我们对1400多个不同的SARS-CoV-2谱系的可解离氨基酸进行了详细分析，证实了这些观察结果，同时表明这种进化在奥密克戎及其亚变体中已达到平稳状态，正电荷不再进一步增加。对核衣壳蛋白的分析表明，新变体的正电荷没有类似的增加，这进一步表明刺突蛋白的正电荷是经过进化选择的。此外，与已知冠状病毒的刺突蛋白比较显示，与大多数其他β冠状病毒相比，野生型SARS-CoV-2刺突蛋白已经携带了异常大量的带正电荷氨基酸。我们的研究揭示了SARS-CoV-2刺突蛋白上可解离氨基酸数量的进化变化，补充了现有研究，并为更好地理解刺突蛋白电荷与病毒感染性和传播性之间的关系提供了一个基础。
