Entamoeba histolytica: from high-throughput technology to new drugs
Anjan Debnath and Sharon L Reed
from: Protozoan Parasitism: From Omics to Prevention and Control (Edited by: Luis Miguel de Pablos Torró and Jacob-Lorenzo Morales). Caister Academic Press, U.K. (2018) Pages: 157-170.
Amebiasis, caused by the protozoan parasite Entamoeba histolytica, is a major contributor to morbidity and mortality worldwide. Current therapy mainly depends on metronidazole, but it is not active against E. histolytica cysts that transmit amebiasis. Therefore, an additional luminal drug paromomycin is required for the treatment. Treatment with two drugs for 20 days leads to incomplete compliance. Moreover, in the absence of a back-up drug and a looming threat of drug resistance, the identification of new drugs for the treatment of amebiasis is a top priority. With the advent of high-throughput screening technology, we focused on developing an assay that could utilize robotics for rapid interrogation of compounds against E. histolytica. We developed a high-throughput screen for E. histolytica and used the validated assay to screen a smaller FDA-approved drug library and a larger kinase-targeted library. The screen of the kinase-targeted library identified six amebicidals and the FDA-approved drug library screen identified auranofin as amebicidal. This opened the avenue for repurposing the anti-arthritic drug, auranofin, for the treatment of amebiasis. Currently, auranofin has completed Phase I clinical trial for amebiasis and is undergoing Phase II clinical trial evaluation for the treatment of amebiasis and giardiasis read more ...