Ribonucleotide reductase as a therapeutic target for drug repurposing as anthelmintics

Exp Parasitol. 2023 Nov 8:108641. doi: 10.1016/j.exppara.2023.108641. Online ahead of print.ABSTRACTVisceral cestodiases, like echinococcoses and cysticercoses, are zoonoses of worldwide distribution and are responsible for public health problems in many countries, especially in underdeveloped regions. Current treatments have low efficiency and there are few drugs currently in use for chemotherapy, making the development of new anthelmintics an urgent matter. The nucleotide salvage pathways are the only ones available for nucleotide synthesis in cestodes and other parasitic helminths, and, here, we used in silico approaches to assess the potential of the enzymes in these pathways as targets for drug repurposing as anthelminthics. First, a genomic survey allowed to identify a repertoire of 28 enzymes of the purine and pyrimidine salvage pathways from the cestode Echinococcus granulosus sensu stricto. Regarding purines, the parasite relies on salvaging free bases rather than salvaging nucleosides. Pyrimidines, on the other hand, can be salvaged from both bases and nucleosides. Druggability of the parasite enzymes was assessed, as well as the availability of commercial inhibitors for them. Druggable enzymes were then ranked according to their potential for drug repurposing and the 17 most promising enzymes were selected for evolutionary analyses. The constructed phylogenetic trees allowed to assess the degree of conservation among ortholog enzymes from parasitic helminths and th...

Source: Experimental Parasitology - November 10, 2023 Category: Parasitology Authors: Marcelo Pasa Panesso Martin Cancela Renato Kulakowski Cor á J éssica Andrade Paes Gabriel Prado Paludo Henrique Bunselmeyer Ferreira Source Type: research