IDENTIFICATION OF NOVEL DRUGS THAT MIMIC LETHAL ANTIBODY BINDING TO PfGARP IN P. FALCIPARUM

The current work investigates the identification of novel drugs that have the potential to be suitable anti-malarials against Plasmodium falciparum-infected erythrocytes. The growing resistance to current therapeutic modalities necessitates the development of new emerging and effective compounds. The target of these compounds in this work will be PfGARP (P. falciparum glutamic-acid-rich protein), a surface antigen of infected erythrocytes (IEs) found only in P. falciparum that has been recently recognized as a valuable drug target and vaccine candidate. Using a two-step approach designed in our lab, we were able to efficiently screen large libraries of small molecules provided by ChemBridge and the Torrey Pines Institute for Molecular Studies (TPIMS). We base the current work on our preliminary results, obtained with a subset of 6,400 compounds of DIVERSet library, reasoning that there may be other individual compounds that can be identified as having equal or greater parasiticidal activity. In this work, initial screening of the ChemBridge DIVERSet library subset of other 3,600 compounds organized into compound mixtures using Bio-Plex technology resulted in the identification of the most active mixtures (HITS-1), which were further deconvoluted into simpler mixtures (HITS-2). Screenings of HITS-2 yielded two mixtures of interest that did not portray any noticeable binding inhibition, and the deconvolution process was thus forfeited.