Host defense peptides in crocodilians – A comprehensive review

Amphibians and reptiles, like all animals, are prone to periodic infections. However, crocodilians stand out for their remarkable ability to remain generally healthy and infection-free despite frequent exposure to a wide variety of microorganisms in their habitats and often sustaining significant injuries. These animals have evolved highly active immune mechanisms that provide rapid and effective defense. This is evidenced by the superior hemolytic capacity of their plasma compared to that of other organisms. To date, several host defense peptides (HDPs) have been identified in crocodilians, including cathelicidins, beta-defensins, hepcidins, leucrocins, hemocidins, and omwaprins. These peptides exhibit potent and broad-spectrum antimicrobial, antibiofilm, antifungal, and anticancer activities. Due to the relatively low but diverse evolutionary rate of crocodilians, the HDPs found in this species offer valuable insights into proteins and mechanisms of action that are highly conserved across many animals related to immune defense. The potential applications of HDPs in modern medicine represent a promising strategy for developing new therapeutic agents. Their novelty and the vast variability with which peptide sequences can be designed and modified expand the field of application for HDPs almost infinitely. This review addresses the urgent need for innovative and more effective drugs to combat the rise of antimicrobialresistant infections and evaluates the potential of crocodilian HDPs. It presents recent advances in the identification of crocodilian HDPs, particularly antimicrobial peptides (AMPs), including previously underexplored topics such as the sequential and structural conformation of different peptide types in crocodilians and the use of bioinformatics tools to enhance native peptides