NEW POTENTIAL
MALARIA TREATMENT DETECTED:
Scientists have discovered a new
molecules that can kill the malaria parasite, paving way for effective
treatment for the disease. Using ultra sophisticated computerized modelling
tools, researchers were successful in identifying a type of candidate molecules
toxic for the pathogen, but not for the infected human red bold cells, the most
severe form of malaria is caused by infection with plasmodium falciparum.
The eradication of this parasite is even more difficult as it becomes resistant to treatments. The group led by Didier Picard from the University of Geneva (UNIGE), Switzerland, showed interest in the protein Heat Shock Protein 90 (HSP90), which plays a central role for several factors involved in the life cycle, survival and resistance of the pathogen. Expressed in organisms as diverse as bacteria and mammal cells, HSP90 acts as a “chaperone”, by helping other proteins during both normal and stressful periods. In the plasmodium, HSP90 protects parasite proteins during high fevers triggered by its presence. The chaperone also participates in the maturation of the pathogen in human red blood cells.
The eradication of this parasite is even more difficult as it becomes resistant to treatments. The group led by Didier Picard from the University of Geneva (UNIGE), Switzerland, showed interest in the protein Heat Shock Protein 90 (HSP90), which plays a central role for several factors involved in the life cycle, survival and resistance of the pathogen. Expressed in organisms as diverse as bacteria and mammal cells, HSP90 acts as a “chaperone”, by helping other proteins during both normal and stressful periods. In the plasmodium, HSP90 protects parasite proteins during high fevers triggered by its presence. The chaperone also participates in the maturation of the pathogen in human red blood cells.
Wang used ultra-sophisticated
computerized modelling tools to characterize the various tridimensional conformations
of the parasite’s HSP90. By studying the HSP90 of the pathogen from every
possible angle, Wang found another pocket capable of binding inhibitory
substances, completely absent in its human alter ego.
Using a supercomputer, he performed
the screening more than a million chemical compounds while retaining those that
could fit in this pocket. This screening in silico led him to select five
candidates. The molecules were thin tested I vitro in different systems.
The biologists demonstrated in
particular the toxicity of those inhibitors on plasmodium falciparum cultures,
In doses sufficient to kill the parasites without affecting the infected red
blood cells.
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