Computational Chemogenomics Drug Repositioning Strategy Enables the Discovery of Epirubicin as a New Repurposed Hit for Plasmodium falciparum and P. vivax

Author:

Ferreira Letícia Tiburcio1,Rodrigues Juliana2,Cassiano Gustavo Capatti13ORCID,Tavella Tatyana Almeida1,Tomaz Kaira Cristina Peralis1,Baia-da-Silva Djane Clarys4,Souza Macejane Ferreira45,Lima Marilia Nunes do Nascimento2,Mottin Melina2,Almeida Ludimila Dias6,Calit Juliana7,Puça Maria Carolina Silva de Barros4,Melo Gisely Cardoso5,Bargieri Daniel Youssef7,Lopes Stefanie Costa Pinto45ORCID,Lacerda Marcus Vinicius Guimarães5,Bilsland Elizabeth6,Sunnerhagen Per8ORCID,Neves Bruno Junior29,Andrade Carolina Horta12,Cravo Pedro Vitor Lemos39,Costa Fabio Trindade Maranhão1ORCID

Affiliation:

1. Laboratory of Tropical Diseases-Prof. Dr. Luiz Jacintho da Silva, Department of Genetics, Evolution, Microbiology and Immunology, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil

2. Laboratory of Molecular Modeling and Drug Design, LabMol, Faculdade de Farmácia, Universidade Federal de Goiás, Goiânia, Goiás, Brazil

3. Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal

4. Instituto Leônidas e Maria Deane, Fundação Oswaldo Cruz–FIOCRUZ, Manaus, Amazonas, Brazil

5. Fundação de Medicina Tropical-Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil

6. Synthetic Biology Laboratory, Department of Structural and Functional Biology, Institute of Biology, UNICAMP, Campinas, São Paulo, Brazil

7. Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo-USP, São Paulo, Brazil

8. Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden

9. LabChem–Laboratory of Cheminformatics, Centro Universitário de Anápolis–UniEVANGÉLICA, Anápolis, Goiás, Brazil

Abstract

Widespread resistance against antimalarial drugs thwarts current efforts for controlling the disease and urges the discovery of new effective treatments. Drug repositioning is increasingly becoming an attractive strategy since it can reduce costs, risks, and time-to-market. Herein, we have used this strategy to identify novel antimalarial hits. We used a comparative in silico chemogenomics approach to select Plasmodium falciparum and Plasmodium vivax proteins as potential drug targets and analyzed them using a computer-assisted drug repositioning pipeline to identify approved drugs with potential antimalarial activity.

Funder

MCTI | Conselho Nacional de Desenvolvimento Científico e Tecnológico

Fundação de Amparo à Pesquisa do Estado de São Paulo

Vetenskapsrådet

MEC | Fundação para a Ciência e a Tecnologia

Instituto Serrapilheira

Fundação de Amparo à Pesquisa do Estado de Goiás

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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