Monogenean parasites constitute a significant threat to the aquaculture industry, primarily infesting fish skin, gills, and fin rays [[1], [2], [3]]. In substantial numbers, not only do they impact fish productivity, but also they cause secondary diseases, resulting in severe economic losses. In particular, Gyrodactylus salaris, a monogenean parasite affecting Atlantic salmon, caused a 50% reduction in young wild Atlantic salmon in two years in Norway, a devastating blow to the salmon farming industry [[4], [5], [6], [7]]. Furthermore, the Benedenia parasite has affected more than 30 families and more than 100 species of fish worldwide, causing considerable economic losses in aquaculture [[8], [9], [10], [11], [12]]. Commonly used parasitic agents in national standards for fisheries include transplant pesticides (such as imidacloprid and fenitrothion), livestock and poultry medicines (such as levamisole and chlorophenylbiguanide), and pharmaceuticals (such as metronidazole and praziquantel). Prolonged and excessive use of these agents has resulted in an increase in parasite resistance, which poses challenges to disease control in aquaculture [13,14]. Consequently, there is an urgent need for the development of natural, environmentally friendly, and non-hazardous pesticides for fisheries.

The primary approaches to antiparasitic drug development include traditional screening, structural modification, and optimization of existing drugs, along with computer-aided drug design. With advances in science and technology, computer-aided drug design based on protein structure has the potential to significantly enhance the success rate and reduce the costs associated with drug development. The discovery of new drugs has been notable, such as those targeting adrenergic receptors [15], potassium channels [16], and sodium-calcium exchange proteins [17]. The researchers, using protein crystal structures, successfully identified new opioid painkillers, demonstrating high efficacy and minimal side effects [18]. The structural resolution of the SARS-CoV-2 proteins facilitated virtual screening, leading to the discovery of pralatrexa with promising antineocoronaviral activity (EC50 = 0.008 μM) targeting RNA-dependent polymerase [19]. In essence, virtual screening of drugs based on key target proteins proves to be a viable shortcut in drug development. Previous research has highlighted the significance of myosin, a crucial structural muscle protein expressed in the helminth tegument. Identifying myosin as our target opens avenues for further inhibitor optimization, paving the way for future drug discovery.

Myosins, a class of enzymes, possess the ability to convert the chemical energy generated through ATP hydrolysis into the mechanical energy essential for life activities. Functioning as linear molecular motors, they have the ability to slide along actin filaments, crucial components of the cytoskeleton. Myosins play a pivotal role in regulating muscle contraction and are involved in various life processes such as substance exchange, signaling, and more in eukaryotes [[20], [21], [22]]. The strong association of myosins with human diseases, including cardiomyopathy, deafness, and cancer, highlights the potential to target specific myosins with inhibitors for the treatment of various dysfunctional diseases [23,24]. The researchers used the available crystal structures of myosin and its inhibitors to design a series of Pseudilin halides with potential myosin ATPase inhibitory activity through computer-assisted and biochemical assays [23,25]. Designing drugs based on myosin emerges as a strategy to quickly access myosin inhibitors. However, the three-dimensional structure of protein-small molecule inhibitor complexes needs resolution, and understanding protein-ligand interactions is a crucial initial step in small molecule drug design and active molecule screening [26,27]. Notably, the myosin of aquatic monogeneans has yet to undergo a protein crystal structure analysis, necessitating the use of computer-homology modeling to conduct interaction studies between the protein and the drug molecule.