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Computational approaches for drug discovery against trypanosomatid-caused diseases

Published online by Cambridge University Press:  12 February 2020

Claudio A. Pereira Open the ORCID record for Claudio A. Pereira [Opens in a new window] ,
Melisa Sayé ,
Chantal Reigada ,
Ariel M. Silber ,
Guillermo R. Labadie ,
Mariana R. Miranda  and
Edward Valera-Vera
Claudio A. Pereira*
Affiliation:
Universidad de Buenos Aires, Facultad de Medicina, Instituto de Investigaciones Médicas A. Lanari, Buenos Aires, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Instituto de Investigaciones Médicas, Laboratorio de Parasitología Molecular, Buenos Aires, Argentina
Melisa Sayé
Affiliation:
Universidad de Buenos Aires, Facultad de Medicina, Instituto de Investigaciones Médicas A. Lanari, Buenos Aires, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Instituto de Investigaciones Médicas, Laboratorio de Parasitología Molecular, Buenos Aires, Argentina
Chantal Reigada
Affiliation:
Universidad de Buenos Aires, Facultad de Medicina, Instituto de Investigaciones Médicas A. Lanari, Buenos Aires, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Instituto de Investigaciones Médicas, Laboratorio de Parasitología Molecular, Buenos Aires, Argentina
Ariel M. Silber
Affiliation:
Laboratory of Biochemistry of Tryps – LaBTryps, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
Guillermo R. Labadie
Affiliation:
Instituto de Química Rosario (IQUIR-CONICET), Universidad Nacional de Rosario, Rosario, Argentina Departamento de Química Orgánica, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.
Mariana R. Miranda
Affiliation:
Universidad de Buenos Aires, Facultad de Medicina, Instituto de Investigaciones Médicas A. Lanari, Buenos Aires, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Instituto de Investigaciones Médicas, Laboratorio de Parasitología Molecular, Buenos Aires, Argentina
Edward Valera-Vera
Affiliation:
Universidad de Buenos Aires, Facultad de Medicina, Instituto de Investigaciones Médicas A. Lanari, Buenos Aires, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Instituto de Investigaciones Médicas, Laboratorio de Parasitología Molecular, Buenos Aires, Argentina
*
Author for correspondence: Claudio A. Pereira, E-mail: [email protected]
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Abstract

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

Type
Review Article
Information
Parasitology , Volume 147 , Issue 6 , May 2020 , pp. 611 - 633
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Copyright © The Author(s), 2020. Published by Cambridge University Press

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