On-virion structural dynamics reveal temperature- and receptor-coordinated activation of an alphacoronavirus spike.

Temperature and hAPN receptor binding coordinate activation of HCoV-229E spike, with RBD-up states promoted at 33°C and prefusion-to-postfusion conversion enhanced at 33°C.

• Why it matters: Human alphacoronaviruses infect the upper respiratory tract, but how physiologic temperature and receptor engagement jointly trigger spike activation is not well defined.
• What they did: Using cryo-electron tomography and subtomogram averaging, the authors visualized HCoV-229E virion spike dynamics at physiologically relevant temperatures, comparing apo conditions and incubation with hAPN.
• The result: They found two reversible prefusion S2 conformations (compact and loose) that interconvert by temperature, and receptor binding stabilizes RBD-up states and promotes prefusion-to-postfusion conversion, especially at 33°C.

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