Receptor-induced activation of MERS-CoV spike revealed by time-course cryo-EM.

Receptor binding induces conformational changes in the MERS-CoV spike that weaken S1-S2 interactions and prime membrane fusion, revealing a structural pathway for activation.

• Why it matters: Understanding how receptor engagement triggers viral fusion is crucial for developing targeted antiviral strategies against MERS-CoV, as the structural coupling remains unclear.
• What they did: Using cryo-electron microscopy, 1, 2, and 3 structures of MERS-CoV spike-DPP4 complexes were captured at different incubation times, revealing conformational states from prefusion to postfusion.
• The result: Findings show receptor binding causes RBD opening, loosening of the S2 core, and spike destabilization, providing a framework for designing interventions that target fusion intermediates.