In silico drug repositioning for chagas disease

Abstract

Chagas disease is an infectious tropical disease included within the group of neglected tropical diseases. Though historically endemic to Latin America, it has lately spread to high-income countries due to human migration. At present, there are only two available drugs, nifurtimox and benznidazole, approved for this treatment, both with considerable side-effects (which often result in treatment interruption) and limited efficacy in the chronic stage of the disease in adults. Drug repositioning involves finding novel therapeutic indications for known drugs, including approved, withdrawn, abandoned and investigational drugs. It is today a broadly applied approach to develop innovative medications, since indication shifts are built on existing safety, ADME and manufacturing information, thus greatly shortening development timeframes. Drug repositioning has been signaled as a particularly interesting strategy to search for new therapeutic solutions for neglected and rare conditions, which traditionally present limited commercial interest and are mostly covered by the public sector and not-for-profit initiatives and organizations. Here, we review the applications of computer-aided technologies as systematic approaches to drug repositioning in the field of Chagas disease. In silico screening represents the most explored approach, whereas other rational methods such as network-based and signature-based approximations have still not been applied.