A new molecule Heat Shock Protein 90 (HSP90) with potential to kill malaria parasite was discovered in the second week of March 2014. The new discovery could help in effective treatment of malaria. The discovery was made by the researchers from the University of Geneva led by Didier Picard.
Team goal was to determine if there was a difference between the human form and the parasitic form of HSP90 and can be used for curative purposes.
Team used sophisticated computerized model tools to characterize the various tridimensional conformations of the parasite’s HSP90. They found another pocket capable of binding inhibitory substances, completely absent in its human alter ego.
Team used supercomputer to perform the screening of virtual library which contains more than a million chemical compounds and selected the five candidates which fit in the pocket of binding inhibitory substances. Virtual screening uses computer-based methods to discover new ligands (ions) on the basis of biological structures.
The simulations were conducted to analyse the dynamics of interaction between the HSP90 and the candidate. This led to the discovery of inhibitors which interact specifically with the Plasmodium falciparum chaperone.
Later the molecules were tested in vitro in different systems. The biologists demonstrated in particular the toxicity of those inhibitors on Plasmodium falciparum cultures, in sufficient doses to kill the parasites without affecting the infected red blood cells.
The Heat Shock Protein 90 (HSP90) plays a central role for several factors involved in the life cycle, survival and resistance of the pathogen. HSP90 acts as a chaperone which helps other proteins during both normal and stressful periods.
During high fever HSP90 protects parasitic proteins in the plasmodium. HSP90 also participates in the maturation of the pathogen in human red blood cells.
• Malaria is a disease caused by a parasite and transmitted by a mosquito. The two parasite species Plasmodium falciparum and Plasmodium vivax cause malaria in humans.
• The parasite multiplies inside red blood cells and liver cells and causes, fever, chills, anemia, vomiting and convulsions. The disease can lead to kidney failure, permanent neurological damage, coma and death.
• The most severe form of malaria is caused by infection with Plasmodium falciparum and eradication of this parasite is even more difficult as it becomes resistant to treatments.