A Short Peptide Inhibitor of Measles Virus Fusion Protein that Exhibits Passive Membrane Permeability

In this study, a passively membrane-permeable short peptide inhibitor targeting the measles virus fusion protein (MeV-F) is reported. Measles virus (MeV) is highly contagious, yet no approved antiviral drugs are currently available. MeV-F plays a crucial role in viral infection, making it an attractive target for drug development. The fusion inhibitor peptide (FIP) is a well-known short peptide that binds to MeV-F and prevents its structural rearrangement. However, improving both inhibitory activity and passive membrane permeability is essential for developing orally available MeV-F inhibitors. Herein, FIP derivatives are explored through hydrogen-to-fluorine substitution and a derivative with enhanced inhibitory activity (IC₅₀ = 90 nM) and passive membrane permeability (P_e = 1.4 × 10^–6 cm s⁻¹) was identified. This study highlights the potential of the long-studied fusion inhibitor peptide as a promising lead compound for the development of orally available drugs against measles infection.