Entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells depends on refolding of the virus-encoded spike protein from a prefusion conformation, metastable after cleavage, to a lower energy, stable postfusion conformation^1,2. This transition overcomes kinetic barriers for fusion of viral and target cell membranes^3,4. We report here a cryo-EM structure of the intact postfusion spike in a lipid bilayer that represents single-membrane product of the fusion reaction. The structure provides structural definition of the functionally critical membrane-interacting segments, including the fusion peptide and transmembrane anchor. The internal fusion peptide forms a hairpin-like wedge that spans almost the entire lipid bilayer and the transmembrane segment wraps around the fusion peptide at the last stage of membrane fusion. These results advance our understanding of the spike protein in a membrane environment and may guide development of intervention strategies.

严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 进入宿主细胞取决于病毒编码的刺突蛋白从裂解后亚稳定的融合前构象重新折叠为能量较低、稳定的融合后构象^1,2 。这种转变克服了病毒和靶细胞膜融合的动力学障碍^3,4 。我们在这里报告了脂质双层中完整的融合后尖峰的冷冻电镜结构，它代表了融合反应的单膜产物。该结构提供了功能关键的膜相互作用片段的结构定义，包括融合肽和跨膜锚。内部融合肽形成发夹状楔形，几乎跨越整个脂质双层，跨膜片段在膜融合的最后阶段包裹在融合肽周围。这些结果增进了我们对膜环境中刺突蛋白的理解，并可能指导干预策略的制定。