Scientists Discover Novel Way of Preventing Malaria Bugs from Breeding
With almost 500,000 deaths and over 200 million new malaria cases worldwide each year, a number of drugs have been devised to deal with the parasitic infection.
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A new international collaboration has now reported that the compound called TCMDC -135051 is capable of stopping the synthesis of a protein required for growth in Plasmodium falciparum, one of the parasites that cause malaria.
According to the study, reported in the journal Science, this could lead to the development of a new antimalarial drug.
The compound inhibits the activity of a parasitic enzyme called protein kinase which regulates RNA splicing and is fundamental to the activity of almost every process within the cell. Furthermore, it does not affect the human form of the enzyme.
With almost 500,000 deaths and over 200 million new malaria cases worldwide each year, a number of drugs have been devised to deal with the parasitic infection. However, resistance develops quickly in most cases. But, in the case of TCMDC - 135051, it affects P. falciparum’s cycle-dependent-like protein kinase PfCLK3 which is a vital enzyme in its lifecycle.
According to study authors, the plasmodial parasite goes through both asexual and sexual phases in its lifecycle. With the asexual mode of reproduction it is able to proliferate and spread to other cells within the body. In the sexual phase it forms gametocytes which can get back into other mosquitoes to complete its development and infect other human beings.
Speaking about the same, Researcher Paulo Godoi said that the inhibition of PfCLK3 affects the parasite in both the asexual stage of its development, when it proliferates in human cells and causes symptoms, and the sexual stage, when it can be transmitted back to the vector insect, repeating the cycle by infecting other humans.
Notably, prior research by the same researcher had produced a list of 36 protein kinase enzymes that are required for the parasite to replicate itself in the blood cells. Among these, they selected a PfCLK3 inhibitor as the target compound, since it was a small molecule and played a key part in regulating cell processes.
The study saw researchers screening almost 25,000 compounds using high-throughput assays to identify molecules with selective inhibition of PfCLK3, before coming to the conclusion that TCMDC-135051 was the most selective and powerful of all the screened molecules.
According to researchers, the new compound could be developed into an extremely potent killer against malarial parasite Plasmodium falciparum due to its ability to arrest the development of the parasite at all stages, whether the blood schizont, the liver schizont or the gametocytic stages.
According to study authors, this occurs because it prevents the splicing of RNA, which carries genetic information out of the nucleus into the cytoplasm; by stopping this, the new compound prevents the production of protein from the parasite’s genes.
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