New medication like compound could adequately hinder a critical step in malaria parasite life cycle

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• Source: The Francis Crick Institute


• Date: 19 May,2021

Researchers at the Francis Crick Institute and the Latvian Institute of Organic Synthesis have designed a drug-like compound which effectively blocks a vital step in the malaria parasite life cycle and are working to develop this compound into a potential first of its type malaria treatment.

While drugs and mosquito control have reduced levels of malaria over recent decades, the parasite still kills over 400,000 people every year, infecting many more. Worryingly, it has now developed resistance to many existing antimalarial drugs, meaning new therapies that work in different ways are desperately needed.

In their research, published in PNAS, the scientists developed a set of chemicals designed to block the parasite being able to burst from red blood cells, a process vital to its replication and life cycle. They found one compound in particular was highly effective in human cell tests.

Malaria parasites invade red blood cells where they replicate many times, before bursting out into the bloodstream to repeat the process. It’s this cycle and build-up of infected red blood cells which causes the symptoms and sometimes fatal effects of the disease. If we can effectively trap malaria in the cell by blocking the parasite’s exit route, we could stop the disease in its tracks and halt its devastating cycle of invading cells.”

Mike Blackman, lead author and group leader of the Malaria Biochemistry Laboratory, Francis Crick Institute

The compound works by blocking an enzyme called SUB1, which is critical for malaria to burst from red blood cells. Present antimalarials work by killing the parasite inside the cell, so the researchers hope this alternate drug action will overcome the resistance the parasite has acquired.

Importantly the compound is also able to pass through the membranes of the red blood cell and of the compartment within the cell at which the parasites live.

The team is continuing to optimize the chemical, which makes it smaller and more potent. If successful, it is going to need to be tested in additional experiments and in human and animal trials to show it’s safe and effective, before being made accessible to people.

Chrislaine Withers-Martinez, author and researcher at the Malaria Biochemistry Laboratory, says:”Many existing antimalarial drugs are plant derived and while they’re incredibly effective, we do not know the exact mechanisms behind how they work. Our years of research have helped us identify and understand pathways crucial to the malaria life cycle allowing us to rationally design new drug compounds based on the structure and mechanics of critical enzymes such as SUB1.

“This strategy, which has already been highly successful at finding new treatments for diseases including HIV and Hepatitis C, could be key to continuing and effective malaria control for many years to come.”