Identification of levothyroxine antichagasic activity through computer-aided drug repurposing

Abstract

Cruzipain (Cz) is the major cysteine protease of the protozoan <i>Trypanosoma cruzi</i>, etiological agent of Chagas disease. A conformation-independent classifier capable of identifying Cz inhibitors was derived from a 163-compound dataset and later applied in a virtual screening campaign on the DrugBank database, which compiles FDA-approved and investigational drugs. 54 approved drugs were selected as candidates, 3 of which were acquired and tested on Cz and <i>T. cruzi</i> epimastigotes proliferation. Among them, levothyroxine, traditionally used in hormone replacement therapy in patients with hypothyroidism, showed dose-dependent inhibition of Cz and antiproliferative activity on the parasite.