Decoding LL-37: Structure and antimicrobial mechanisms against microbial threats

INTRODUCTION: The emergence of antibiotic-resistant pathogens is a significant global health concern that necessitates the development of new antimicrobial drugs. Due to its broad-spectrum action against bacteria, fungi, and viruses, human cathelicidin LL-37, an antimicrobial peptide (AMP), has emerged as a potential option. METHODS: Data from PubMed, Scopus, Google Scholar, and Web of Science up to March 30, 2025, were investigated in this study. Studies were considered depending on their analysis of LL-37's structure, antimicrobial abilities, and mechanisms of action. For bacterial, fungal, and viral infections, standardized tests produced quantitative data. RESULTS: LL-37 effectively combats over 38 bacteria, 16 fungi, and 16 viruses through various mechanisms, including membrane rupture, targeting, and biofilm suppression. These mechanisms involve cell wall destruction, membrane permeabilization, oxidative stress, cell cycle arrest, adhesion prevention, gene modification, and disruption of viral envelopes, entry, and replication. CONCLUSION: LL-37 presents a potential medicinal possibility due to its broad-spectrum antimicrobial properties. However, issues such as proteolytic sensitivity and potential high-concentration toxicity must be addressed. To fully realize LL-37's therapeutic potential against multidrug-resistant infections, future studies should focus on creating stable analogs, optimizing delivery mechanisms, and exploring synergistic combinations with existing antibiotics.