A Systematic In Silico Search for Target Similarity Identifies Several Approved Drugs with Potential Activity against the Plasmodium falciparum Apicoplast

A Systematic In Silico Search for Target Similarity Identifies Several Approved Drugs with Potential Activity against the Plasmodium falciparum Apicoplast

Most of the drugs in use against Plasmodium falciparum share similar modes of action and, consequently, there is a need to identify alternative potential drug targets. Here, we focus on the apicoplast, a malarial plastid-like organelle of algal source which evolved through secondary endosymbiosis. W...

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Main Authors: Bispo, Nadlla Alves, Culleton, Richard, Silva, Lourival Almeida, Cravo, Pedro
Format: Online
Language:English
Published: Public Library of Science 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608639/
id pubmed-3608639
recordtype oai_dc
spelling pubmed-36086392013-04-03 A Systematic In Silico Search for Target Similarity Identifies Several Approved Drugs with Potential Activity against the Plasmodium falciparum Apicoplast Bispo, Nadlla Alves Culleton, Richard Silva, Lourival Almeida Cravo, Pedro Research Article Most of the drugs in use against Plasmodium falciparum share similar modes of action and, consequently, there is a need to identify alternative potential drug targets. Here, we focus on the apicoplast, a malarial plastid-like organelle of algal source which evolved through secondary endosymbiosis. We undertake a systematic in silico target-based identification approach for detecting drugs already approved for clinical use in humans that may be able to interfere with the P. falciparum apicoplast. The P. falciparum genome database GeneDB was used to compile a list of ≈600 proteins containing apicoplast signal peptides. Each of these proteins was treated as a potential drug target and its predicted sequence was used to interrogate three different freely available databases (Therapeutic Target Database, DrugBank and STITCH3.1) that provide synoptic data on drugs and their primary or putative drug targets. We were able to identify several drugs that are expected to interact with forty-seven (47) peptides predicted to be involved in the biology of the P. falciparum apicoplast. Fifteen (15) of these putative targets are predicted to have affinity to drugs that are already approved for clinical use but have never been evaluated against malaria parasites. We suggest that some of these drugs should be experimentally tested and/or serve as leads for engineering new antimalarials. Public Library of Science 2013-03-26 /pmc/articles/PMC3608639/ /pubmed/23555651 http://dx.doi.org/10.1371/journal.pone.0059288 Text en © 2013 Bispo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Bispo, Nadlla Alves
Culleton, Richard
Silva, Lourival Almeida
Cravo, Pedro
spellingShingle Bispo, Nadlla Alves
Culleton, Richard
Silva, Lourival Almeida
Cravo, Pedro
A Systematic In Silico Search for Target Similarity Identifies Several Approved Drugs with Potential Activity against the Plasmodium falciparum Apicoplast
author_facet Bispo, Nadlla Alves
Culleton, Richard
Silva, Lourival Almeida
Cravo, Pedro
author_sort Bispo, Nadlla Alves
title A Systematic In Silico Search for Target Similarity Identifies Several Approved Drugs with Potential Activity against the Plasmodium falciparum Apicoplast
title_short A Systematic In Silico Search for Target Similarity Identifies Several Approved Drugs with Potential Activity against the Plasmodium falciparum Apicoplast
title_full A Systematic In Silico Search for Target Similarity Identifies Several Approved Drugs with Potential Activity against the Plasmodium falciparum Apicoplast
title_fullStr A Systematic In Silico Search for Target Similarity Identifies Several Approved Drugs with Potential Activity against the Plasmodium falciparum Apicoplast
title_full_unstemmed A Systematic In Silico Search for Target Similarity Identifies Several Approved Drugs with Potential Activity against the Plasmodium falciparum Apicoplast
title_sort systematic in silico search for target similarity identifies several approved drugs with potential activity against the plasmodium falciparum apicoplast
description Most of the drugs in use against Plasmodium falciparum share similar modes of action and, consequently, there is a need to identify alternative potential drug targets. Here, we focus on the apicoplast, a malarial plastid-like organelle of algal source which evolved through secondary endosymbiosis. We undertake a systematic in silico target-based identification approach for detecting drugs already approved for clinical use in humans that may be able to interfere with the P. falciparum apicoplast. The P. falciparum genome database GeneDB was used to compile a list of ≈600 proteins containing apicoplast signal peptides. Each of these proteins was treated as a potential drug target and its predicted sequence was used to interrogate three different freely available databases (Therapeutic Target Database, DrugBank and STITCH3.1) that provide synoptic data on drugs and their primary or putative drug targets. We were able to identify several drugs that are expected to interact with forty-seven (47) peptides predicted to be involved in the biology of the P. falciparum apicoplast. Fifteen (15) of these putative targets are predicted to have affinity to drugs that are already approved for clinical use but have never been evaluated against malaria parasites. We suggest that some of these drugs should be experimentally tested and/or serve as leads for engineering new antimalarials.
publisher Public Library of Science
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608639/
_version_ 1611965505515552768

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