Discovery of New Potent anti-MERS CoV Fusion Inhibitors

Area of Science:

• Virology
• Drug Discovery
• Biochemistry

Background:

• Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus causing severe pneumonia in humans.
• Viral fusion is a critical step in MERS-CoV infection, making it a target for antiviral development.

Purpose of the Study:

• To design and evaluate novel peptides that inhibit MERS-CoV fusion by targeting the HR1 binding site.
• To assess the potency and safety of these designed peptides as potential antiviral agents.

Main Methods:

• Eleven peptides were designed to compete with heptad repeat domain 2 (HR2) at the HR1 binding site.
• Inhibition of MERS-CoV cell-cell fusion was measured using IC50 values.
• MERS-CoV plaque formation was assessed to evaluate antiviral efficacy.
• Cytotoxicity assays were performed to determine peptide safety.

Main Results:

• Eight peptides demonstrated potent inhibition of MERS-CoV cell-cell fusion with nanomolar IC50 values.
• Peptides #4-6 significantly inhibited MERS-CoV plaque formation (95-98.3%).
• Peptide four showed strong inhibition with an EC50 of 0.302 µM.
• All tested peptides were non-cytotoxic up to 10 µM.

Conclusions:

• The designed peptides are potent inhibitors of MERS-CoV fusion and viral replication.
• These peptides exhibit promising antiviral activity and a safe cellular profile.
• The developed peptides represent potential therapeutic candidates for MERS-CoV infection.