Monogeneans are a group of parasitic flatworms that primarily infect fish. These parasites have a direct and typically brief life cycle. Adults produce eggs that hatch into infectious larvae called oncomiracidia, which reach juvenile and adult stages once anchored to fish hosts. The eggs of some monogenean species have filaments that get tangled in net cages, increasing the infection rate in aquaculture systems. The attachment of monogeneans to the host can lead to mucus overproduction, epithelial damage, hemorrhaging, osmotic imbalances, and gill atrophy (Ogawa, 2015). The Gyrodactylidae, Dactylogyridae, Diplectanidae, and Capsalidae families include some pathogenic species (Thoney, 1990; Ogawa, 2015). For instance, Gyrodactylus salaris, from the Gyrodactylidae family, is classified by the World Organization for Animal Health as a pathogen causing severe effects on salmon populations, highlighting its significant impact on the sector. Neobenedenia melleni, of the Capsalidae family, is known for causing diseases and increasing mortality in various globally farmed marine fish species (Whittington, 2012). Within the family Diplectanidae, Diplectanum aequans affects European seabass, Dicentrarchus labrax (Tokşen et al., 2013), and Rhabdosynochus viridisi has been linked to mortality events in broodstocks of Pacific white snook, Centropomus viridis, at the fish pilot plant of the Food and Development Research Center in Mazatlán (CIAD-Mazatlán) in northwestern Mexico (Morales-Serna et al., 2020a).

In the absence of vaccines, the control of monogenean infections in aquaculture focuses on the use of chemical treatments (Ogawa, 2015). Although several control methods exist against monogeneans, such as the application of formalin, albendazole, or praziquantel in baths, these are not always totally effective; therefore, alternative methods are required (Morales-Serna et al., 2018; Mladineo et al., 2021; Tu et al., 2021). Recently, plumbagin, a phytochemical compound, was found to be a potent antimonogenean agent against Gyrodactylus kobayashii (Tu et al., 2021). In addition, compared to praziquantel, plumbagin seems to be a more effective anthelmintic agent to control the trematode Schistosoma mansoni, one of the parasites causing human schistosomiasis (Lorsuwannarat et al., 2013). Based on these findings, it is possible that the effectiveness of plumbagin spans to a wider range of monogenean species.

Just like plumbagin, there are a plethora of natural and synthetic compounds that can be evaluated as antimonogeneans; nonetheless, testing each one could be time-consuming and require the use of experimental fish systems. One alternative to developing antiparasitic drugs is the computer-guided drug repositioning approach. Drug repositioning refers to applying an existing compound with a defined therapeutic indication to treat a different disease and offers a practical method to find new therapies (Oprea and Overington, 2015). This strategy offers a greater probability of success when working with drugs already approved by the FDA, since these compounds have gone through the development stages in which their pharmacokinetic properties and toxicity are evaluated (Saldívar-González et al., 2017). Drug repositioning can take advantage of the analysis of genomic, transcriptomic, proteomic, and pharmacological data (Akhoon et al., 2019; Fernández-Prada et al., 2019). There are several computational methods available for drug repositioning, encompassing target-based, knowledge-based, signature-based, network-based, and targeted-mechanism-based approaches (Kulkarni et al., 2023). The target-based method, widely used in drug repositioning, relies on the availability of structural data for ligands or receptors. This method involves in silico screening of compounds using docking or pharmacophore models, enabling the exploration of drug interactions (Akhoon et al., 2019). In molecular docking, the process starts with selecting a biological target, acquiring or modeling its three-dimensional structure. Subsequently, drugs are chosen to simulate their interaction with the selected target, thus assessing their therapeutic potential. This approach has not been used to identify antimonogenean compounds, but it has been used to identify anthelmintics against trematodes. For instance, Giuliani et al. (2018) filtered 97 drugs approved by the FDA, of which 11 had an antiparasitic effect against juveniles and five against adults of Schistosoma japonicum.

Thus, the present study aimed to apply a computer-guided drug repositioning method in the search for novel antimonogenean treatments. Of the predicted compounds, it was possible to evaluate in vitro the antimonogenean efficacy of bromocriptine against the monogenean R. viridisi (Diplectanidae). The efficacy of plumbagin against this parasite was also evaluated. R. viridisi is considered a threat to the production of Pacific white snook (C. viridis) in northwestern Mexico (Morales-Serna et al., 2020a)