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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Autores principales:	Nadlla Alves Bispo, Richard Culleton, Lourival Almeida Silva, Pedro Cravo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/783ca260b4d34a4ca9d0d331ba6d833f
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spelling	oai:doaj.org-article:783ca260b4d34a4ca9d0d331ba6d833f2021-11-18T07:52:02ZA systematic in silico search for target similarity identifies several approved drugs with potential activity against the Plasmodium falciparum apicoplast.1932-620310.1371/journal.pone.0059288https://doaj.org/article/783ca260b4d34a4ca9d0d331ba6d833f2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23555651/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Most 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.Nadlla Alves BispoRichard CulletonLourival Almeida SilvaPedro CravoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e59288 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nadlla Alves Bispo Richard Culleton Lourival Almeida Silva Pedro Cravo A 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.
format	article
author	Nadlla Alves Bispo Richard Culleton Lourival Almeida Silva Pedro Cravo
author_facet	Nadlla Alves Bispo Richard Culleton Lourival Almeida Silva Pedro Cravo
author_sort	Nadlla Alves Bispo
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.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/783ca260b4d34a4ca9d0d331ba6d833f
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A systematic in silico search for target similarity identifies several approved drugs with potential activity against the Plasmodium falciparum apicoplast.

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