Structural transition and antibody binding of Ebola GP and Zika E proteins from pre-fusion to fusion-initiation state

Membrane fusion proteins are responsible for viral entry into host cells -- a crucial first step in viral infection. These proteins undergo large conformational changes from pre-fusion to fusion initiation structures, and, despite differences in viral genomes and disease etiology, many fusion proteins are arranged as trimers. Structural information for both pre-fusion and fusion initiation states is critical for understanding virus neutralization by the host immune system. In the case of Ebola glycoprotein (GP) and Zika envelope protein (Zika E), pre-fusion state structures have been identified experimentally, but only partial structures of fusion initiation states have been described. While the fusion initiation structure is in an energetically unfavorable state that is difficult to solve experimentally, the existing structural information combined with computational approaches enabled the modeling of fusion initiation state structures of both proteins. These structural models provide an improved understanding of four different neutralizing antibodies in the prevention of viral host entry.