Fatal measles virus infection prevented by brain-penetrant fusion inhibitors

Area of Science:

• Virology
• Neuroscience
• Drug Discovery

Background:

• Measles virus (MV) causes acute childhood illness, potentially leading to severe neurological disease without effective treatments.
• Central nervous system involvement and rare progressive neurological complications highlight the need for novel therapeutic strategies.

Purpose of the Study:

• To develop potent antiviral peptide inhibitors targeting MV entry, spreading, and cell fusion.
• To evaluate the efficacy of these peptide inhibitors in protecting against fatal MV infection.

Main Methods:

• Generation of MV-specific peptide dimers derived from the MV fusion protein's C-terminal heptad repeat region.
• Conjugation of peptides to cholesterol to enhance delivery and efficacy.
• Testing in SLAM transgenic mouse models of fatal MV infection.

Main Results:

• Cholesterol-conjugated peptide dimers demonstrated potent inhibition of MV entry and cell fusion.
• These peptide inhibitors efficiently protected SLAM transgenic mice from lethal MV infection.
• The study identified effective fusion inhibitors for MV.

Conclusions:

• Antiviral peptide fusion inhibitors are effective against measles virus infection.
• These inhibitors hold significant promise for measles prophylaxis in vulnerable populations.
• Potential applications include treatment for severe neurological complications of measles.