Summary Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, along with the threat of a future coronavirus-mediated pandemic, underscore the importance of finding ways to combat these viruses. The trimeric spike transmembrane glycoprotein S mediates entry into host cells and is the major target of neutralizing antibodies. To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors. Although the two antibodies studied blocked attachment to the host cell receptor, only the anti-SARS-CoV S antibody triggered fusogenic conformational changes via receptor functional mimicry. These results provide a structural framework for understanding coronavirus neutralization by human antibodies and shed light on activation of coronavirus membrane fusion, which takes place through a receptor-driven ratcheting mechanism. Graphical Abstract Highlights • MERS-CoV/SARS-CoV S composite glycan shields analyzed by cryo-EM and mass spectrometry • Structures of MERS-CoV/SARS-CoV S with neutralizing antibodies from survivors • LCA60 inhibits receptor binding by interacting with MERS-CoV S protein/glycans • S230 blocks receptor binding and triggers fusogenic rearrangements via functional mimicry Structural analysis of the SARS-CoV S and MERS-CoV S glycoproteins in complex with neutralizing antibodies from human survivors sheds light into the mechanisms of membrane fusion and neutralization
【저자키워드】 coronavirus, Neutralizing antibodies, SARS-CoV, spike glycoprotein, MERS-CoV, membrane fusion, glycoproteomics, N-linked glycosylation, class I fusion protein,