Unlocking the therapeutic potential of AMPs: From mechanism to future research approaches

Antibiotic resistance is currently one of the largest threats to human health. A common family of naturally occurring substances with broad-spectrum antipathogenic activity, antimicrobial peptides (AMPs), has great potential as a useful remedy for the current antibiotic resistance problem. Numerous AMPs are currently in the pharmacological development pipeline, and several others have been identified and assessed for their potential therapeutic applications. They exert their antimicrobial effects through membrane disruption, interference with intracellular processes, and immunomodulatory activities, with their functional outcomes strongly influenced by key structural features. We delve into the structure–activity relationship of AMPs, emphasizing how parameters such as amino acid composition, charge, hydrophobicity, and secondary structure govern their efficacy and selectivity. The integration of bioinformatics and molecular dynamics simulations has revolutionized the rational design of AMPs by enabling detailed insights into peptide–membrane interactions, conformational dynamics, and stability. Despite their potential, challenges such as toxicity, stability, and high production costs remain. The review concludes with future perspectives, highlighting the role of machine learning, peptide engineering, and hybrid therapeutic strategies in overcoming current limitations and advancing AMPs toward widespread clinical use.