Engineered Human Cathelicidin Antimicrobial Peptides Inhibit Ebola Virus Infection

Area of Science:

• Virology and Microbiology
• Drug Discovery and Development
• Infectious Diseases

Background:

• The 2014-2016 West Africa Ebola virus (EBOV) outbreak and subsequent outbreaks highlight the urgent need for effective EBOV treatments.
• Developing diverse countermeasures is crucial to combat the high lethality of EBOV infections.

Purpose of the Study:

• To investigate the potential of human cathelicidin antimicrobial peptide (AMP) LL-37 and its engineered variants as novel anti-EBOV therapeutics.
• To explore the mechanism by which AMPs inhibit EBOV infection.

Main Methods:

• Utilized recombinant viruses pseudotyped with EBOV glycoprotein (GP) and wild-type EBOV for infection assays.
• Tested the inhibitory effects of LL-37 and engineered LL-37 AMPs on EBOV infection.
• Investigated the impact of AMPs on the endosomal cell-entry step and cathepsin B-mediated processing of EBOV GP.

Main Results:

• Human cathelicidin AMP LL-37 and engineered LL-37 AMPs effectively inhibited EBOV infection.
• AMPs interfere with EBOV infection at the endosomal cell-entry stage by impairing cathepsin B-mediated EBOV GP processing.
• Engineered AMPs containing D-amino acids exhibited superior potency, likely due to increased resistance to degradation.

Conclusions:

• Antimicrobial peptides (AMPs) represent a novel class of potential therapeutics against Ebola virus.
• Engineering AMPs, particularly those with D-amino acids, can enhance their efficacy against EBOV.
• These findings support the development of AMP-based strategies for combating EBOV.