» Articles » PMID: 37089958

Omics Data Integration Facilitates Target Selection for New Antiparasitic Drugs Against TriTryp Infections

Overview
Journal Front Pharmacol
Date 2023 Apr 24
PMID 37089958
Authors
Affiliations
Soon will be listed here.
Abstract

, , and , commonly referred to as TriTryps, are a group of protozoan parasites that cause important human diseases affecting millions of people belonging to the most vulnerable populations worldwide. Current treatments have limited efficiencies and can cause serious side effects, so there is an urgent need to develop new control strategies. Presently, the identification and prioritization of appropriate targets can be aided by integrative genomic and computational approaches. In this work, we conducted a genome-wide multidimensional data integration strategy to prioritize drug targets. We included genomic, transcriptomic, metabolic, and protein structural data sources, to delineate candidate proteins with relevant features for target selection in drug development. Our final ranked list includes proteins shared by TriTryps and covers a range of biological functions including essential proteins for parasite survival or growth, oxidative stress-related enzymes, virulence factors, and proteins that are exclusive to these parasites. Our strategy found previously described candidates, which validates our approach as well as new proteins that can be attractive targets to consider during the initial steps of drug discovery.

Citing Articles

Understanding Host-Pathogen Interactions in Congenital Chagas Disease Through Transcriptomic Approaches.

Caceres T, Patino L, Ramirez J Pathogens. 2025; 14(2).

PMID: 40005483 PMC: 11858232. DOI: 10.3390/pathogens14020106.


Metallomics: An Essential Tool for the Study of Potential Antiparasitic Metallodrugs.

Machado I, Gambino D ACS Omega. 2024; 9(14):15744-15752.

PMID: 38617611 PMC: 11007724. DOI: 10.1021/acsomega.3c10200.

References
1.
de Matos Guedes H, Carneiro M, Gomes D, Rossi-Bergmann B, De-Simone S . Oligopeptidase B from Leishmania amazonensis: molecular cloning, gene expression analysis and molecular model. Parasitol Res. 2007; 101(4):865-75. DOI: 10.1007/s00436-007-0630-8. View

2.
Fenno J, Lee S, Bayer C, Ning Y . The opdB locus encodes the trypsin-like peptidase activity of Treponema denticola. Infect Immun. 2001; 69(10):6193-200. PMC: 98751. DOI: 10.1128/IAI.69.10.6193-6200.2001. View

3.
Willert E, Phillips M . Cross-species activation of trypanosome S-adenosylmethionine decarboxylase by the regulatory subunit prozyme. Mol Biochem Parasitol. 2009; 168(1):1-6. PMC: 2730992. DOI: 10.1016/j.molbiopara.2009.05.009. View

4.
Jensen R, Englund P . Network news: the replication of kinetoplast DNA. Annu Rev Microbiol. 2012; 66:473-91. DOI: 10.1146/annurev-micro-092611-150057. View

5.
Yokoyama K, Trobridge P, Buckner F, Scholten J, Stuart K, Van Voorhis W . The effects of protein farnesyltransferase inhibitors on trypanosomatids: inhibition of protein farnesylation and cell growth. Mol Biochem Parasitol. 1998; 94(1):87-97. DOI: 10.1016/s0166-6851(98)00053-x. View