冠状病毒 z-bio 2021-02-21 356

　　Recently, a team composed of Professor Peng Guiqing from the State Key Laboratory of Agricultural Microbiology of Huazhong Agricultural University and Shanghai University of Science and Technology analyzed the atomic degradation structure of the surface-labeled protein (S) of coronavirus 229E (HCoV-). Capturing the two intermediate conformations of the spiny spine protein reveals the dynamic conformational changes required for HCoV-229E to invade host cells, and provides a new idea for the development of coronavirus vaccines. "Nature Communications" has published the results online. There are many types of coronaviruses, which seriously threaten the safety of public health and the healthy development of animal husbandry worldwide. Among them, the coronaviruses that infect mammals are mainly alpha-coronaviruses (HCoV-229E, PEDV, TGEV, FIPV, etc.). And beta coronavirus (SARS-CoV, SARS-CoV-2, MERS-CoV). Coronavirus Peplomer (S) is a homotrimer, which plays an important role in mediating virus invasion and inducing the production of neutralizing antibodies. Studies have shown that the β-coronavirus S protein receptor binding domain (RBD) has a transition from a "lying" conformation to a "standing" conformation, thereby completing the binding to cell receptors. However, how the α-coronavirus S protein RBD binds to its receptor through a conformational switch has always been an open scientific question. The

　　 group used single-particle cryo-electron microscope three-dimensional reconstruction technology to analyze the structure of the two conformations of HCoV-229E peplomer. Configuration 1 is a "thin" structure in which all three receptor binding regions (RBD) are "lying". Due to steric hindrance, it cannot bind to the receptor APN. This conformation is inactive for receptor binding. State (closed state).

　　 At the same time, the researchers discovered a new "short and thick" configuration with loose RBD positions. It promotes conversion to a "standing" state and binds to receptors.

　　 This discovery can be extended to other coronaviruses (PEDV, TGEV, FIPV) that seriously endanger animal health. It has important scientific significance in understanding the molecular mechanism of invading host cells and developing new vaccines and drugs. On this basis, Peng Guiqing’s research team designed and expressed the coronavirus S-trimmer and S-RBD, and through the evaluation of the immune effect, proposed the development idea of the coronavirus subunit vaccine: α-coronavirus (HCoV-229E, PEDV, for example, Etc.), S-trimer is more suitable as subunit vaccine than S-RBD; for β-coronavirus (SARS-CoV and SARS-CoV-2), S-trimer and S-RBD are both used as subunit vaccine .