Inhibitors of Protein Targets of Plasmodium falciparum

The World Health Organization documented 247 million reported malaria cases worldwide resulting in 619,000 fatalities in 2021. More than 70% of these deaths are attributed to Children under five years of age and sub-Saharan Africa is the region in which the highest number of deaths occur. The Plasmo...

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Main Authors: Solomon Uche Oranusi, Emmanuel Ojochegbe Mameh, Samuel Adeniyi Oyegbade, Daniel Oluwatobiloba Balogun, Victoria-Grace Onyekachi Aririguzoh
Format: Article
Language:English
Published: Journal of Pure and Applied Microbiology 2024-12-01
Series:Journal of Pure and Applied Microbiology
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Online Access:https://microbiologyjournal.org/inhibitors-of-protein-targets-of-plasmodium-falciparum/
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author Solomon Uche Oranusi
Emmanuel Ojochegbe Mameh
Samuel Adeniyi Oyegbade
Daniel Oluwatobiloba Balogun
Victoria-Grace Onyekachi Aririguzoh
author_facet Solomon Uche Oranusi
Emmanuel Ojochegbe Mameh
Samuel Adeniyi Oyegbade
Daniel Oluwatobiloba Balogun
Victoria-Grace Onyekachi Aririguzoh
author_sort Solomon Uche Oranusi
collection DOAJ
description The World Health Organization documented 247 million reported malaria cases worldwide resulting in 619,000 fatalities in 2021. More than 70% of these deaths are attributed to Children under five years of age and sub-Saharan Africa is the region in which the highest number of deaths occur. The Plasmodium falciparum parasite is the deadliest form of malaria, and treating falciparum infection is becoming more challenging due to the emergence of drug-resistant parasites, causing a decrease in the efficiency of antimalarial medications. Artemisinin combination therapy is now considered the gold standard for malaria treatment; however, this method is at risk due to parasites exhibiting delayed clearance to artemisinin and resistance to partner drugs such as lumefantrine, amodiaquine, mefloquine, piperaquine, and sulfadoxine/pyrimethamine. This review assessed drug targets in Plasmodium falciparum for the development of novel antimalarials. Over Eighty-five papers on malaria, Plasmodium falciparum protein targets, and protein inhibitors were gathered from Google Scholar, ProQuest, PubMed, and Science Direct, between 2012 and 2023. Only articles with comparable keywords on malaria drug targets concentrating on enzyme proteins, carrier molecules present in Plasmodium falciparum, and their inhibitors were retrieved for review, while articles within that range that did not provide definite data were excluded. Most recently, inhibitors of dihydroorotate dehydrogenase (DHODH), artefenomel (OZ439), and ferroquine have been reported and are being explored in combination with other partner medications to work against different stages of plasmodium parasite. In identifying target proteins for drug development, essentiality and vulnerability throughout the life cycle of the parasite, its druggability, and the availability of target-based assays are critical factors. The use of modern proteomics and cellular proteins from database search which assists in parasite proliferation delivers optimal information on the new generation of lead compounds. In addition, advances in in silico methods enable the identification of protein targets for drug development.
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spelling doaj-art-5564bcfa20424f83a3fd0a581ad1b10b2025-08-20T01:55:00ZengJournal of Pure and Applied MicrobiologyJournal of Pure and Applied Microbiology0973-75102581-690X2024-12-0118421512162https://doi.org/10.22207/JPAM.18.4.36Inhibitors of Protein Targets of Plasmodium falciparumSolomon Uche Oranusihttps://orcid.org/0000-0002-5594-6683Emmanuel Ojochegbe Mamehhttps://orcid.org/0009-0005-2247-9942Samuel Adeniyi Oyegbadehttps://orcid.org/0009-0009-7853-0654Daniel Oluwatobiloba Balogunhttps://orcid.org/0000-0002-5399-098XVictoria-Grace Onyekachi Aririguzohhttps://orcid.org/0009-0009-5245-0859The World Health Organization documented 247 million reported malaria cases worldwide resulting in 619,000 fatalities in 2021. More than 70% of these deaths are attributed to Children under five years of age and sub-Saharan Africa is the region in which the highest number of deaths occur. The Plasmodium falciparum parasite is the deadliest form of malaria, and treating falciparum infection is becoming more challenging due to the emergence of drug-resistant parasites, causing a decrease in the efficiency of antimalarial medications. Artemisinin combination therapy is now considered the gold standard for malaria treatment; however, this method is at risk due to parasites exhibiting delayed clearance to artemisinin and resistance to partner drugs such as lumefantrine, amodiaquine, mefloquine, piperaquine, and sulfadoxine/pyrimethamine. This review assessed drug targets in Plasmodium falciparum for the development of novel antimalarials. Over Eighty-five papers on malaria, Plasmodium falciparum protein targets, and protein inhibitors were gathered from Google Scholar, ProQuest, PubMed, and Science Direct, between 2012 and 2023. Only articles with comparable keywords on malaria drug targets concentrating on enzyme proteins, carrier molecules present in Plasmodium falciparum, and their inhibitors were retrieved for review, while articles within that range that did not provide definite data were excluded. Most recently, inhibitors of dihydroorotate dehydrogenase (DHODH), artefenomel (OZ439), and ferroquine have been reported and are being explored in combination with other partner medications to work against different stages of plasmodium parasite. In identifying target proteins for drug development, essentiality and vulnerability throughout the life cycle of the parasite, its druggability, and the availability of target-based assays are critical factors. The use of modern proteomics and cellular proteins from database search which assists in parasite proliferation delivers optimal information on the new generation of lead compounds. In addition, advances in in silico methods enable the identification of protein targets for drug development.https://microbiologyjournal.org/inhibitors-of-protein-targets-of-plasmodium-falciparum/malariaresistancedrug targetsdrug developmentsub-saharan africaplasmodium falciparum
spellingShingle Solomon Uche Oranusi
Emmanuel Ojochegbe Mameh
Samuel Adeniyi Oyegbade
Daniel Oluwatobiloba Balogun
Victoria-Grace Onyekachi Aririguzoh
Inhibitors of Protein Targets of Plasmodium falciparum
Journal of Pure and Applied Microbiology
malaria
resistance
drug targets
drug development
sub-saharan africa
plasmodium falciparum
title Inhibitors of Protein Targets of Plasmodium falciparum
title_full Inhibitors of Protein Targets of Plasmodium falciparum
title_fullStr Inhibitors of Protein Targets of Plasmodium falciparum
title_full_unstemmed Inhibitors of Protein Targets of Plasmodium falciparum
title_short Inhibitors of Protein Targets of Plasmodium falciparum
title_sort inhibitors of protein targets of plasmodium falciparum
topic malaria
resistance
drug targets
drug development
sub-saharan africa
plasmodium falciparum
url https://microbiologyjournal.org/inhibitors-of-protein-targets-of-plasmodium-falciparum/
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AT emmanuelojochegbemameh inhibitorsofproteintargetsofplasmodiumfalciparum
AT samueladeniyioyegbade inhibitorsofproteintargetsofplasmodiumfalciparum
AT danieloluwatobilobabalogun inhibitorsofproteintargetsofplasmodiumfalciparum
AT victoriagraceonyekachiaririguzoh inhibitorsofproteintargetsofplasmodiumfalciparum