Researchers from the Francis Crick Institute and the Latvian Institute for Organic Synthesis have designed a drug-like compound that effectively blocks a critical stage in the life cycle of the malaria parasite and are working to develop this compound as a first treatment potential of this type against malaria.
While drugs and mosquito control have reduced malaria levels over the past decades, the parasite still kills more than 400,000 people each year, infecting many more. Worryingly, he has now developed resistance to many existing antimalarial drugs, which means that new treatments that work in different ways are urgently needed.
In their research, published in PNAS, scientists have developed a set of compounds designed to prevent the parasite from leaving red blood cells, a process vital for its replication and lifecycle. They found that one compound in particular was very effective in human cell tests.
“Malaria parasites invade red blood cells where they replicate several times, before spreading into the bloodstream to repeat the process. It is this cycle and the accumulation of infected red blood cells that causes the symptoms and sometimes the effects. fatal from the disease, ”says Mike Blackman, senior author and group leader of the Malaria Biochemistry Lab at Crick.
“If we can effectively trap malaria in the cell by blocking the parasite’s escape route, we could stop the disease in its tracks and stop its devastating cycle of invading cells.
The compound works by blocking an enzyme called SUB1, which is essential for malaria to get out of red blood cells. Existing antimalarials work by killing the parasite in the cell, so the researchers hope this alternative drug action will overcome the resistance the parasite has acquired.
It is important to note that the compound is also able to pass through the membranes of the red blood cell and the compartment inside the cell where the parasites reside.
The team continues to optimize the compound, making it smaller and more potent. If successful, it will need to be tested in other experiments and in animal and human trials to show that it is safe and effective, before it is made available to people.
Chrislaine Withers-Martinez, author and researcher at the Malaria Biochemistry Laboratory, says: “Many of the antimalarial drugs out there are plant-based and although they are incredibly effective, we don’t know the precise mechanisms behind how they work. Our decades of research have helped us identify and understand critical pathways for the malaria lifecycle, which has enabled us to rationally design new drug compounds based on the structure and mechanism of critical enzymes such as SUB1.
“This approach, which has already been very successful in finding new treatments for diseases such as HIV and hepatitis C, could be the key to a sustainable and effective fight against malaria for many years to come.”
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