Computational approaches for drug discovery against trypanosomatid caused diseases

PEREIRA, CA; SAYE, MELISA; REIGADA, CHANTAL; SILBER, ARIEL; LABADIE, GUILLERMO; VALERA-VERA, EDWARD

PARASITOLOGY

CAMBRIDGE UNIV PRESS

Lugar: Cambridge; Año: 2020

0031-1820

23 During three decades, only about 20 new drugs have been developed for malaria,24 tuberculosis and all neglected tropical diseases (NTDs). This critical situation was25 reached because NTDs represents only 10% of health research investments,26 however, they comprise about 90% of the global disease burden. Computational27 simulations applied in virtual screening (VS) strategies are very efficient tools to28 identify pharmacologically active compounds or new indications for drugs already29 administered for other diseases. One of the advantages of this approach is the low30 time-consuming and low-budget first stage, which filters for testing experimentally a31 group of candidate compounds with high chances of binding to the target and32 present trypanocidal activity. In this work, we review the most common VS strategies33 that have been used for the identification of new drugs with special emphasis on34 those applied to trypanosomiasis and leishmaniasis. Computational simulations35 based on the selected protein targets or their ligands are explained, including the36 method selection criteria, examples of successful VS campaigns applied to NTDs, a37 list of validated molecular targets for drug development, and repositioned drugs for38 trypanosomatid caused diseases. Thereby, here we present the state-of-the-art of39 VS and drug repurposing to conclude pointing out the future perspectives in the field.