Antimicrobial Peptides: Mechanisms, Applications, and Therapeutic Potential.

Abstract

Antimicrobial peptides (AMPs) are short protein fragments that function as an innate immune response across diverse life forms. Structurally, AMPs exhibit diverse configurations, including α-helical, β-sheet, mixed, and random-coil forms, enabling a variety of mechanisms to combat pathogens. The mechanisms of action of AMPs encompass membrane disruption and inhibition of critical cellular processes, highlighting their broad-spectrum activity against bacteria, fungi, viruses, and parasites. AMP activity extends to anti-tumor and anti-HIV activities, further emphasizing their therapeutic potential. Purifying AMPs from natural sources can be challenging due to posttranslational processing. Fortunately, chemical synthesis has the advantage of producing high yield and pure AMPs, but the reaction efficiency diminishes as the molecular weight of peptides increases. Advances in computational tools and curated databases have further accelerated AMP discovery and engineering. While commercially available AMP-based antibiotics and in vivo efficacy against multidrug-resistant bacteria demonstrate their clinical relevance, several limitations still hinder the widespread use of AMPs such as low stability and toxicity to human cells. This review provides a comprehensive overview of AMP origins, characteristics, mechanisms, applications, and future prospects in combating infectious diseases with a particular focus on the clinical applicability of AMPs and their prospects as potent alternative to traditional antibiotics.