Screening and Identification of Pathogen Box® Compounds with anti-Trypanosoma evansi Activity.

The research aims to identify new potential drugs from the Pathogen Box® library that could combat Trypanosoma evansi, a pathogen causing diseases in horses and other animals predominantly in Asia and South America. Of the 400 compounds screened, five demonstrated anti-T.evansi activity in vitro, with the compound MMV688410 showing particular promise due to its presumed mechanism of action.

Overview of Research Objetive and Methodology

• This research study is focused on identifying new potential drugs that could combat Trypanosoma evansi (T. evansi), a pathogen causing neglected diseases in animals.
• T. evansi is particularly widespread in Asia and South America. It has significant economic impact by reducing animal productivity and causing death.
• The researchers used Pathogen Box®, a library consisting of 400 different molecules created by the Medicines for Malaria Venture (MMV). The aim of Pathogen Box® is to speed up the identification of potential drugs to fight neglected diseases.
• The researchers evaluated the in vitro activity of these 400 compounds against T. evansi.

Principal Findings

• Out of 400 compounds, 5 were found to have anti-T. evansi activity. These were pentamidine, MMV688410, MMV687273, MMV022478, and auranofin.
• Surprisingly, suramin which is noted as a trypanocidal activity molecule in the Pathogen Box® reference compound list, did not demonstrate any anti-T. evansi activity in the in vitro assays.
• The research highlighted MMV688410 as the most promising candidate. It not only induced death in T. evansi, but also reduced the number of parasites in cell culture.
• The potential effectiveness of MMV688410 is likely due to its inhibition of the trypanosomal reductase enzyme. This is significant because this enzyme is a unique target of trypanosomatides—a group that T. evansi belongs to.

Looking Forward

• The authors recommend further in vitro and in vivo testing to confirm the efficacy of the identified compounds, especially MMV688410.
• Additional factors to consider during further testing include the drugs’ ability to penetrate the blood-brain barrier since T. evansi can invade the central nervous system, and their tissue distribution.