Elucidation of Postfusion Structures of the Measles Virus F Protein for the Structure-Based Design of Fusion Inhibitors.

Abstract

Measles is a highly infectious disease and remains a major cause of childhood mortality worldwide. In some cases, the measles virus (MV) induces subacute sclerosing panencephalitis within several years of the acute infection. The infection of the target cells by MV is mediated by the F protein, in which two heptad repeat regions, HR1 and HR2, form a six-helix bundle before membrane fusion. We previously reported anti-MV peptides, which were designed from the HR region of the MV F protein. Here, we characterized the essential interactions between the HR1 and HR2 regions on the postfusion six-helix bundles of synthetic HR1 and HR2 peptides by crystallographic studies. Based on the crystal structures, we identified the minimal α-helix sequence for antiviral activity. Additionally, optimizing HR2 peptides by introducing α-helix-inducible motifs and maintaining key hydrogen bond networks at the N- and C-terminal regions led to the identification of highly potent antiviral peptides.