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

Authors

Yajie Wang, Xiyuan Pan, Yuxuan Jiang, Zhimin Liu, Yinong Qiu, Zhenguo Chen, Lei Sun

Published in

PLoS pathogens. Volume 22. Issue 10. Pages e1014545. Epub Oct 08, 2026.

Abstract

The Middle East respiratory syndrome coronavirus (MERS-CoV) initiates infection by engaging its host receptor dipeptidyl peptidase 4 (DPP4), which activates the viral spike (S) glycoprotein. However, how receptor binding is structurally coupled to membrane fusion has remained unclear. Here, using cryo-electron microscopy, we determined structures of MERS-CoV spike-DPP4 complexes at defined incubation times, capturing a series of conformational states spanning prefusion, receptor-bound, and postfusion conformations. These structures reveal that receptor-binding domain (RBD) opening progressively weakens S1-S2 interactions, while DPP4 binding may induce conformational drift and loosening of the S2 fusion core. These structural changes might destabilize spike trimers, promote S1 dissociation, and prime the fusion machinery. Compared with the SARS-CoV-2 spike, the MERS-CoV spike exhibits greater conformational plasticity, consistent with a lower threshold for receptor-induced fusion. In addition, the postfusion S2 structure suggests that the HR2 upstream linker may function as a conformational switch during six-helix bundle assembly. Together, these findings outline a structural pathway. for receptor-induced activation of the MERS-CoV spike and provide a structural framework for the development of antiviral strategies targeting dynamic fusion intermediates.

PMID:
42848779
Bibliographic data and abstract were imported from PubMed on 09 Oct 2026.

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