{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:49:51Z","timestamp":1792788591412,"version":"4.5.0"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82394463"],"award-info":[{"award-number":["82394463"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"R&D Program of Guangzhou Laboratory","award":["SRPG22-003"],"award-info":[{"award-number":["SRPG22-003"]}],"id":[{"id":"https:\/\/ror.org\/03ybmxt82","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Key R&D Program of China","award":["2021YFC2302500"],"award-info":[{"award-number":["2021YFC2302500"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>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\u2013electron 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.<\/jats:p>","DOI":"10.1371\/journal.ppat.1014545","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:22:36Z","timestamp":1791480156000},"page":"e1014545","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Receptor-induced activation of MERS-CoV spike revealed by time-course cryo-EM"],"prefix":"10.1371","volume":"22","author":[{"given":"Yajie","family":"Wang","sequence":"first","affiliation":[{"name":"Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University","place":["Shanghai, China"],"department":["Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Fifth People\u2019s Hospital"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyuan","family":"Pan","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University","place":["Shanghai, China"],"department":["Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Fifth People\u2019s Hospital"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University","place":["Shanghai, China"],"department":["Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Fifth People\u2019s Hospital"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhimin","family":"Liu","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University","place":["Shanghai, China"],"department":["Shanghai Institute 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