NIH Grantees Discover Malaria Parasites Use Unique Metabolic Pathway, Uncovering Potential New Drug Targets
A newly described metabolic pathway used by malaria-causing parasites may help them survive inside human blood cells. The finding, by researchers supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, clarifies the picture of parasite metabolism and provides clues to potential weak points in the pathway that might be attacked with drugs. In most living things, several major chemical processes involved in converting food to energy are linked through a cyclic hub called the tricarboxylic acid cycle, also known as the Krebs cycle. NIAID grantee Manuel Llinás, Ph.D., of Princeton University, and his colleagues discovered that Plasmodium falciparum, the deadliest malaria parasite, uses a double-branched metabolic pathway instead of the classical loop. According to Dr. Llinás, this specific branched pathway has not been detected previously in any other organism.
The malaria parasite appears to use one branch primarily to generate the molecule acetyl-CoA, which it needs to thrive within a host organism. This branch may represent particularly vulnerable spots to target with anti-malarial drugs, says Dr. Llinás. The detailed description of the chemical steps involved in the metabolic pathway of the malaria parasite also could aid future malaria drug development efforts because the pathway sits at the heart of several other biological processes currently being investigated as drug targets. So far, it is clear that the newly discovered pathway operates while the parasites are growing inside human blood cells. Next, the scientists will explore whether the parasite uses the same pathway during other stages of its lifecycle in humans and in mosquitoes, and how exactly it is involved in the metabolic control of the cell.
Nature. DOI: 10.1038/nature09301 (2010).
http://www.niaid.nih.gov/news/newsreleases/2010/Pages/malariaMetabolism.aspx
Showing posts with label EMBL-EBI. malaria parasite. Show all posts
Showing posts with label EMBL-EBI. malaria parasite. Show all posts
Monday, 9 August 2010
Thursday, 20 May 2010
MALARIA: Research on chemicals
Geneva, 20 May 2010. In an unprecedented move, data from three new projects supported by Medicines for Malaria Venture (MMV) have been made available in the public domain. The first, conducted by GlaxoSmithKline (GSK) has identified promising leads to develop new antimalarials. The second, the screening of compounds of the Genomics Institute of the Novartis Research Foundation (GNF) has been released to the European Bioinformatics Institute (EMBL-EBI). The third, conducted by Prof. Kip Guy at St Jude Children’s Research Hospital, Memphis, will also be released to the EMBL-EBI this week.
The GSK research comes from a year-long screening of more than 2 million compounds in GSK’s chemical library to identify those that could inhibit the malaria parasite, P. falciparum, and reports on an analysis of over 13,500 compounds that showed greatest activity. The largest group of compounds whose mode of action is understood was kinase inhibitors. The study also identified compounds that might be inhibiting processes in human red blood cells necessary for the parasite's survival. This opens up a novel possibility of fighting infection by halting these processes rather than stopping the malaria parasite itself.
All these data are available online through the European Bioinformatics Institute (EMBL-EBI) http://www.ebi.ac.uk/chemblntd/download, Collaborative Drug Discovery http://www.collaborativedrug.com/ and PubChem from the National Library of Medicine (NIH) http://pubchem.ncbi.nlm.nih.gov/ . Together with added intelligence from a publication in Nature[1], scientists globally have been given thousands of chemical starting points to stimulate their research into this deadly disease.
Data from part of an earlier screen from the Genomics Institute of the Novartis Research Foundation are also being reported. Over 800,000 compounds from external sources were screened, and over 5,600 compounds have confirmed activity on the parasite. The chemical structures of these compounds, the 50% inhibitory concentrations against P. falciparum growth, and general cytotoxicity have also recently been released to the EMBL-EBI.
The GSK research comes from a year-long screening of more than 2 million compounds in GSK’s chemical library to identify those that could inhibit the malaria parasite, P. falciparum, and reports on an analysis of over 13,500 compounds that showed greatest activity. The largest group of compounds whose mode of action is understood was kinase inhibitors. The study also identified compounds that might be inhibiting processes in human red blood cells necessary for the parasite's survival. This opens up a novel possibility of fighting infection by halting these processes rather than stopping the malaria parasite itself.
All these data are available online through the European Bioinformatics Institute (EMBL-EBI) http://www.ebi.ac.uk/chemblntd/download, Collaborative Drug Discovery http://www.collaborativedrug.com/ and PubChem from the National Library of Medicine (NIH) http://pubchem.ncbi.nlm.nih.gov/ . Together with added intelligence from a publication in Nature[1], scientists globally have been given thousands of chemical starting points to stimulate their research into this deadly disease.
Data from part of an earlier screen from the Genomics Institute of the Novartis Research Foundation are also being reported. Over 800,000 compounds from external sources were screened, and over 5,600 compounds have confirmed activity on the parasite. The chemical structures of these compounds, the 50% inhibitory concentrations against P. falciparum growth, and general cytotoxicity have also recently been released to the EMBL-EBI.
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