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

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.