The SARS-CoV-2 S protein on the membrane of infected cells can promote receptor-dependent syncytia formation, relating to extensive tissue damage and lymphocyte elimination. In this case, it is challenging to obtain neutralizing antibodies and prevent them through antibodies effectively. Considering that, in the current study, structural domain search methods are adopted to analyze the SARS-CoV-2 S protein to find the fusion mechanism. The results show that after the EF-hand domain of S protein bound to calcium ions, S2 protein had CaMKII protein activities. Besides, the CaMKII_AD domain of S2 changed S2 conformation, facilitating the formation of HR1-HR2 six-helix bundles. Apart from that, the Ca²⁺-ATPase of S2 pumped calcium ions from the virus cytoplasm to help membrane fusion, while motor structures of S drove the CaATP_NAI and CaMKII_AD domains to extend to the outside and combined the viral membrane and the cell membrane, thus forming a calcium bridge. Furthermore, the phospholipid-flipping-ATPase released water, triggering lipid mixing and fusion and generating fusion pores. Then, motor structures promoted fusion pore extension, followed by the cytoplasmic contents of the virus being discharged into the cell cytoplasm. After that, the membrane of the virus slid onto the cell membrane along the flowing membrane on the gap of the three CaATP_NAI. At last, the HR1-HR2 hexamer would fall into the cytoplasm or stay on the cell membrane. Therefore, the CaMKII_like system of S protein facilitated membrane fusion for further inducing syncytial multinucleated giant cells.

受感染细胞膜上的 SARS-CoV-2 S 蛋白可促进受体依赖性合胞体的形成，与广泛的组织损伤和淋巴细胞消除有关。在这种情况下，获得中和抗体并通过抗体有效地预防它们具有挑战性。考虑到，在目前的研究中，采用结构域搜索的方法来分析SARS-CoV-2 S蛋白以寻找融合机制。结果表明，S蛋白的EF-hand结构域与钙离子结合后，S2蛋白具有CaMKII蛋白活性。此外，S2的CaMKII_AD结构域改变了S2的构象，促进了HR1-HR2六螺旋束的形成。除此之外，Ca ²⁺S2的-ATPase从病毒细胞质中泵出钙离子帮助膜融合，而S的运动结构驱动CaATP_NAI和CaMKII_AD结构域向外延伸，结合病毒膜和细胞膜，从而形成钙桥。此外，磷脂翻转 ATP 酶释放水，引发脂质混合和融合并产生融合孔。然后，运动结构促进融合孔延伸，随后病毒的细胞质内容物被释放到细胞质中。之后，病毒的膜在三个CaATP_NAI的间隙上沿着流动的膜滑到细胞膜上。最后，HR1-HR2六聚体落入细胞质或留在细胞膜上。所以，