Identifying potential drug targets in the kinomes of two monogenean species.

Protein kinases are enzymes involved in essential biological processes such as signal transduction, transcription, metabolism, and the cell cycle. Human kinases are targets for several drugs approved by the US Food and Drug Administration. Therefore, the identification and classification of kinases in other organisms, including pathogenic parasites, is an interesting subject of study. Monogeneans are platyhelminths, mainly ectoparasites, capable of causing health problems in farmed fish. Although some genomes and transcriptomes are available for monogenean species, their full repertoire of kinases is unknown. The aim of this study was to identify and classify the putative kinases in the transcriptomes of two monogeneans, Rhabdosynochus viridisi and Scutogyrus longicornis, and then to predict potential monogenean drug targets (MDTs) and selective inhibitor drugs using computational approaches. Monogenean kinases having orthologs in the lethal phenotype of C. elegans but not in fish or humans were considered MDTs. A total of 160 and 193 kinases were identified in R. viridisi and S. longicornis, respectively. Of these, 22 kinases, belonging mainly to the major groups CAMK, AGC, and TK, were classified as MDTs, five of which were evaluated further. Molecular docking analysis indicated that dihydroergotamine, ergotamine, and lomitapide have the highest affinity for the kinases BRSK and MEKK1. These well-known drugs could be evaluated in future studies for potential repurposing as anti-monogenean agents. The present study contributes valuable data for the development of new antiparasitic candidates for finfish aquaculture.

In silico identification of tetraspanins in monopisthocotylean (Platyhelminthes: Monogenea) parasites of fish.

Tetraspanins are a superfamily of transmembrane proteins that in flatworms have structural roles in the development, maturation or stability of the tegument. Several tetraspanins are considered as potential candidates for vaccines or drugs against helminths. Monopisthocotylean monogeneans are ectoparasites of fish that are health hazards for farmed fish. The aim of this study was to identify in silico putative tetraspanins in the genomic datasets of four monopisthocotylean species. The analysis predicted and classified 40 tetraspanins in Rhabdosynochus viridisi, 39 in Scutogyrus longicornis, 22 in Gyrodactylus salaris and 13 in Neobenedenia melleni, belonging to 13 orthologous groups. The high divergence of tetraspanins made it difficult to annotate their function. However, a conserved group was identified in different metazoan taxa. According to this study, metazoan tetraspanins can be divided into 17 monophyletic groups. Of the 114 monogenean tetraspanins, only seven were phylogenetically close to tetraspanins from non-platyhelminth metazoans, which suggests that this group of proteins shows rapid sequence divergence. The similarity of the monopisthocotylean tetraspanins was highest with trematodes, followed by cestodes and then free-living platyhelminths. In total, 27 monopisthocotylean-specific and 34 flatworm-specific tetraspanins were identified. Four monogenean tetraspanins were orthologous to TSP-1, which is a candidate for the development of vaccines and a potential pharmacological target in trematodes and cestodes. Although studies of tetraspanins in parasitic flatworms are scarce, this is an interesting group of proteins for the development of new methods to control monogeneans.

Mitochondrial genome of Rhabdosynochus viridisi (Monogenea: Diplectanidae), a parasite of Pacific white snook Centropomus viridis.

We report the nearly complete mitochondrial genome of Rhabdosynochus viridisi - the first for this genus - achieved by combining shotgun sequencing of genomic and cDNA libraries prepared using low-input protocols. This integration of genomic information leads us to correct the annotation of the gene features. The mitochondrial genome consists of 13,863 bp. Annotation resulted in the identification of 12 protein-encoding genes, 22 tRNA genes and two rRNA genes. Three non-coding regions, delimited by three tRNAs, were found between the genes nad5 and cox3. A phylogenetic analysis grouped R. viridisi with three other species of diplectanid monogeneans for which mitochondrial genomes are available.