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Analysing the essential proteins set of Plasmodium falciparum PF3D7 for novel drug targets identification against malaria
BACKGROUND: Plasmodium falciparum is an obligate intracellular parasite of humans that causes malaria. Falciparum malaria is a major public health threat to human life responsible for high mortality. Currently, the risk of multi-drug resistance of P. falciparum is rapidly increasing. There is a need...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336052/ https://www.ncbi.nlm.nih.gov/pubmed/34344361 http://dx.doi.org/10.1186/s12936-021-03865-1 |
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author | Ali, Fawad Wali, Hira Jan, Saadia Zia, Asad Aslam, Muneeba Ahmad, Imtiaz Afridi, Sahib Gul Shams, Sulaiman Khan, Asifullah |
author_facet | Ali, Fawad Wali, Hira Jan, Saadia Zia, Asad Aslam, Muneeba Ahmad, Imtiaz Afridi, Sahib Gul Shams, Sulaiman Khan, Asifullah |
author_sort | Ali, Fawad |
collection | PubMed |
description | BACKGROUND: Plasmodium falciparum is an obligate intracellular parasite of humans that causes malaria. Falciparum malaria is a major public health threat to human life responsible for high mortality. Currently, the risk of multi-drug resistance of P. falciparum is rapidly increasing. There is a need to address new anti-malarial therapeutics strategies to combat the drug-resistance threat. METHODS: The P. falciparum essential proteins were retrieved from the recently published studies. These proteins were initially scanned against human host and its gut microbiome proteome sets by comparative proteomics analyses. The human host non-homologs essential proteins of P. falciparum were additionally analysed for druggability potential via in silico methods to possibly identify novel therapeutic targets. Finally, the PfAp4AH target was prioritized for pharmacophore modelling based virtual screening and molecular docking analyses to identify potent inhibitors from drug-like compounds databases. RESULTS: The analyses identified six P. falciparum essential and human host non-homolog proteins that follow the key druggability features. These druggable targets have not been catalogued so far in the Drugbank repository. These prioritized proteins seem novel and promising drug targets against P. falciparum due to their key protein–protein interactions features in pathogen-specific biological pathways and to hold appropriate drug-like molecule binding pockets. The pharmacophore features based virtual screening of Pharmit resource predicted a lead compound i.e. MolPort-045–917-542 as a promising inhibitor of PfAp4AH among prioritized targets. CONCLUSION: The prioritized protein targets may worthy to test in malarial drug discovery programme to overcome the anti-malarial resistance issues. The in-vitro and in-vivo studies might be promising for additional validation of these prioritized lists of drug targets against malaria. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12936-021-03865-1. |
format | Online Article Text |
id | pubmed-8336052 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-83360522021-08-04 Analysing the essential proteins set of Plasmodium falciparum PF3D7 for novel drug targets identification against malaria Ali, Fawad Wali, Hira Jan, Saadia Zia, Asad Aslam, Muneeba Ahmad, Imtiaz Afridi, Sahib Gul Shams, Sulaiman Khan, Asifullah Malar J Research BACKGROUND: Plasmodium falciparum is an obligate intracellular parasite of humans that causes malaria. Falciparum malaria is a major public health threat to human life responsible for high mortality. Currently, the risk of multi-drug resistance of P. falciparum is rapidly increasing. There is a need to address new anti-malarial therapeutics strategies to combat the drug-resistance threat. METHODS: The P. falciparum essential proteins were retrieved from the recently published studies. These proteins were initially scanned against human host and its gut microbiome proteome sets by comparative proteomics analyses. The human host non-homologs essential proteins of P. falciparum were additionally analysed for druggability potential via in silico methods to possibly identify novel therapeutic targets. Finally, the PfAp4AH target was prioritized for pharmacophore modelling based virtual screening and molecular docking analyses to identify potent inhibitors from drug-like compounds databases. RESULTS: The analyses identified six P. falciparum essential and human host non-homolog proteins that follow the key druggability features. These druggable targets have not been catalogued so far in the Drugbank repository. These prioritized proteins seem novel and promising drug targets against P. falciparum due to their key protein–protein interactions features in pathogen-specific biological pathways and to hold appropriate drug-like molecule binding pockets. The pharmacophore features based virtual screening of Pharmit resource predicted a lead compound i.e. MolPort-045–917-542 as a promising inhibitor of PfAp4AH among prioritized targets. CONCLUSION: The prioritized protein targets may worthy to test in malarial drug discovery programme to overcome the anti-malarial resistance issues. The in-vitro and in-vivo studies might be promising for additional validation of these prioritized lists of drug targets against malaria. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12936-021-03865-1. BioMed Central 2021-08-03 /pmc/articles/PMC8336052/ /pubmed/34344361 http://dx.doi.org/10.1186/s12936-021-03865-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Ali, Fawad Wali, Hira Jan, Saadia Zia, Asad Aslam, Muneeba Ahmad, Imtiaz Afridi, Sahib Gul Shams, Sulaiman Khan, Asifullah Analysing the essential proteins set of Plasmodium falciparum PF3D7 for novel drug targets identification against malaria |
title | Analysing the essential proteins set of Plasmodium falciparum PF3D7 for novel drug targets identification against malaria |
title_full | Analysing the essential proteins set of Plasmodium falciparum PF3D7 for novel drug targets identification against malaria |
title_fullStr | Analysing the essential proteins set of Plasmodium falciparum PF3D7 for novel drug targets identification against malaria |
title_full_unstemmed | Analysing the essential proteins set of Plasmodium falciparum PF3D7 for novel drug targets identification against malaria |
title_short | Analysing the essential proteins set of Plasmodium falciparum PF3D7 for novel drug targets identification against malaria |
title_sort | analysing the essential proteins set of plasmodium falciparum pf3d7 for novel drug targets identification against malaria |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336052/ https://www.ncbi.nlm.nih.gov/pubmed/34344361 http://dx.doi.org/10.1186/s12936-021-03865-1 |
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