Abstract

One of the major health challenges in Chile's salmon industry is infestation by the ectoparasite Caligus rogercresseyi. Current treatments, primarily organophosphate compounds targeting acetylcholinesterase (AChE), are increasingly limited by resistance. This study investigates antimicrobial peptides (AMPs) from Atlantic salmon (Salmo salar) skin mucus as a potential alternative with lower risk of resistance and reduced environmental impact. Using a combination of in silico and in vitro approaches, a QSAR model screened 959 peptides, predicting 21 candidates with AChE inhibitory activity (IC50 < 100 mu M). These peptides were chemically synthesized and evaluated for antiparasitic activity against C. rogercresseyi nauplius, along with hemolytic and cytotoxic effects on salmon cells. Four peptides inhibited the nauplius stage with EC50 values ranging from 3 to 31 mu M at 48 and 72 h post-exposure. Among them, AS4532, AS4531, and AS4528 were confirmed as competitive AChE inhibitors, with Ki values of 64.8, 72.7, and 98.6 mu M, respectively. Notably, none of the peptides induced hemolysis or cytotoxicity. These findings provide the first evidence that fish mucus peptides can act as effective antiparasitic agents targeting AChE in C. rogercresseyi, offering a promising alternative to conventional chemical treatments.