Cryo-EM analysis of the HCoV-229E spike glycoprotein reveals dynamic prefusion conformational changes

Coronaviruses spike (S) glycoproteins mediate viral entry into host cells by binding to host receptors. However, how the S1 subunit undergoes conformational changes for receptor recognition has not been elucidated in Alphacoronavirus. Here, we report the cryo-EM structures of the HCoV-229E S trimer in prefusion state with two conformations. The activated conformation may pose the potential exposure of the S1-RBDs by decreasing of the interaction area between the S1-RBDs and the surrounding S1-NTDs and S1-RBDs compared to the closed conformation. Furthermore, structural comparison of our structures with the previously reported HCoV-229E S structure showed that the S trimers trended to open the S2 subunit from the closed conformation to open conformation, which could promote the transition from pre- to postfusion. Our results provide insights into the mechanisms involved in S glycoprotein-mediated Alphacoronavirus entry and have implications for vaccine and therapeutic antibody design.
The spike protein of coronaviruses (S-protein) is an envelope-anchored trimeric type I transmembrane glycoprotein that mediates receptor binding and the fusion of the viral and host cell membranes. Here the authors report the conformational states of HCoV-229E S trimer and observe the conformational changes in S1 subunit from closed state to activated state for receptor binding.