A new compound that blocks a critical step in the malaria parasite lifecycle could be the key to a new treatment, British scientists have reported.
Researchers at the Francis Crick Institute, UK, and the Latvian Institute of Organic Synthesis say their design stops the parasite being able to burst out of red blood cells, which is vital to its replication and life cycle.
Writing in the latest PNAS, they say one compound was particularly effective in human cell tests.
Lead author Mike Blackman, group leader of the Malaria Biochemistry Laboratory at the Crick Institute, said: “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.”
The compound blocks the SUB1 enzyme and can also pass through the membranes of the red blood cell and of the compartment within the cell where the parasites reside.
Study author Chrislaine Withers-Martinez, of the Malaria Biochemistry Laboratory, says: “Many existing antimalarial drugs are plant derived and while they’re incredibly effective, we don’t know the precise mechanisms behind how they work. Our decades 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 mechanism of critical enzymes like SUB1.
“This approach, which has already been highly successful at finding new treatments for diseases including HIV and Hepatitis C, could be key to sustained and effective malaria control for many years to come.”
The team is working to make the compound smaller and more potent.
Lidumniece E, Withers-Martinez C, Hackett F et al. Peptidic boronic acids are potent cell-permeable inhibitors of the malaria parasite egress serine protease SUB1. PNAS 10 May 2021
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