Human coronavirus 229E (HCoV‐229E) usually causes mild upper respiratory infections in heathy adults, but may lead to severe complications or mortality in individuals with weakened immune systems. Virus entry of HCoV‐229E is mediated by its spike (S) protein, where the S1 domain facilitates attachment to host cells and the S2 domain is involved in subsequent fusion of the virus and host membranes. During the fusion process, two heptad repeats, HR1 and HR2, in the S2 domain assemble into a six‐helix membrane‐fusion structure termed the fusion core. Here, the complete fusion‐core structure of HCoV‐229E has been determined at 1.86 Å resolution, representing the most complete post‐fusion conformation thus far among published human alphacoronavirus (α‐HCoV) fusion‐core structures. The overall structure of the HCoV‐229E fusion core is similar to those of SARS, MERS and HCoV‐NL63, but the packing of its 3HR1 core differs from those of SARS and MERS in that it contains more noncanonical `x’ and `da’ layers. Side‐by‐side electrostatic surface comparisons reveal that the electrostatic surface potentials are opposite in α‐HCoVs and β‐HCoVs at certain positions and that the HCoV‐229E surface also appears to be the most hydrophobic among the various HCoVs. In addition to the highly conserved hydrophobic interactions between HR1 and HR2, some polar and electrostatic interactions are also well preserved across different HCoVs. This study adds to the structural profiling of HCoVs to aid in the structure‐based design of pan‐coronavirus small molecules or peptides to inhibit viral fusion. The complete post‐fusion core structure of the Human coronavirus 229E spike protein was determined at 1.86 Å resolution. Comparison of the interactions between heptad repeats HR1 and HR2 in different human coronaviruses reveals some differences, which should be taken into consideration when designing pan‐coronavirus HR2‐mimicking inhibitors that target HR1.
【저자키워드】 coronavirus, SARS, MERS, Spike protein, X‐ray structure, HCoV‐229E, post‐fusion core, 【초록키워드】 Mortality, Human, peptide, virus, Protein, Adults, comparison, Mild, small molecule, inhibitor, Interaction, structures, host cell, individual, upper respiratory infection, hydrophobic, immune systems, S2 domain, opposite, S1 domain, coronavirus 229E, heptad repeat, Complete, electrostatic interaction, weakened, surface potential, human coronavirus, conserved, involved, subsequent, addition, inhibit, facilitate, appear, was determined, cause, representing, reveal, electrostatic, severe complication, polar, host membranes, hydrophobic interaction, preserved, 【제목키워드】 Human, crystal structure, coronavirus 229E,