4E Interacting Protein as a Potential Novel Drug Target for Nucleoside Analogues in Trypanosoma Bruce

Human African trypanosomiasis is a neglected parasitic disease for which the current
treatment options are quite limited. Trypanosomes are not able to synthesize purines de novo and
thus solely depend on purine salvage from the host environment. This characteristic makes players
of the purine salvage pathway putative drug targets. The activity of known nucleoside analogues
such as tubercidin and cordycepin led to the development of a series of C7-substituted nucleoside
analogues. Here, we use RNA interference (RNAi) libraries to gain insight into the mode-of-action
of these novel nucleoside analogues. Whole-genome RNAi screening revealed the involvement of
adenosine kinase and 4E interacting protein into the mode-of-action of certain antitrypanosomal
nucleoside analogues. Using RNAi lines and gene-deficient parasites, 4E interacting protein was
found to be essential for parasite growth and infectivity in the vertebrate host. The essential nature
of this gene product and involvement in the activity of certain nucleoside analogues indicates that it
represents a potential novel drug target.

Jaar van publicatie:2021

Toegankelijkheid:Open