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Chemists Develop Novel Drug to Fight Malaria

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Malaria Red Blood Cells

Malaria “ a mosquito borne disease is one of the deadly diseases to affect mankind; it kills more than 500,000 people annually. A team of researchers led by scientists from the University of Washington and two other institutions has some great news to share. They have created a new compound that can strengthen the fight against malaria and the compound is ready for human trials.

The research paper was published in Science Translational Medicine recently. The news revealed that this compound has the capacity to cripple a critical protein which is essential for the malaria parasite to survive at different stages of its complex life cycle. If the said clinical trials on humans are successful, the compound known by its acronym DSM265”could equip the doctors with a new tool to prevent and treat infection by the microscopic parasites that cause malaria. This novel anti-malarial drug is the team's first major breakthrough for use in humans.

The team made great efforts to identify and optimize chemical compounds that show promise against malaria parasites. The scientists in this research belong to various international institutes”spanning 20 institutions on three continents. They pooled their collective expertise and accelerated the pace of discovery and validation.

UW chemistry professor Pradipsinh Rathod, one of the founders and leaders of this research project said that this is the first of a new class of molecules that’s going into humans. Till date, everything used against malaria had been variations of the drugs that were developed in the distant past.

DSM265 acts on a cellular protein – known by its acronym DHODH- made by the malaria parasite. This protein is critical for the malaria parasite to express their genes and copy them when it’s time to divide. Since, the role of DHODH is a critical one for these parasites; this drug could impair the parasite at multiple stages of its life cycle “ one of the most important being when it hides in the human host’s liver.

All the enabling chemistry work was done at Rathod's UW lab and all the tests on malaria parasite cells and human cells started and have continued there. Scientists had long sought drugs that would inactivate DHODH. The Texas researchers studied the malaria DHODH protein, and worked on identifying a chemical compound that would cripple it. When they found a chemical that seemed promising, Rathod’s lab undertook validation, modification, and fine-tuning. With additional able guidance and collaboration from advisors at the Medicines for Malaria Venture, Rathod’s group altered the chemical compound to increase its potency against DHODH. Rathod's group made more than 500 versions of the initial compound and the found the 265th “ DSM265 “ to be most promising.

‘DSM’ stands for ‘Dallas-Seattle-Melbourne,’ the three cities where the founding teams were working on this project. The DSM265 and related compounds were then passed onto their collaborators at Monash University, who tested how human cells might modify or metabolize the compound. They carried out experiments to ensure that a drug based on DSM265 would last long enough in our bodies for a single-dose anti-malarial treatment. Rathod’s lab also developed and performed experiments to test how well the malaria parasite might evolve to become resistant against DSM265. If the conditions that permit the malaria parasite to develop resistance to DSM265 are known, the drug’s use can be tailored in a clinical setting to lower that risk.

Rathod has high hopes that the development and discovery pipeline for DSM265 will make the way for a faster and more collaborative drug development process in the long war against the deadly disease.