To combat the growing resistance of malaria to current treatments, researchers at the Francis Crick Institute and the Latvian Institute of Organic Synthesis have designed a new antimalarial compound which interrupts the malaria parasite life cycle by trapping them in their host cells.
While drugs and mosquito control have reduced levels of malaria over recent decades, with malaria being effectively wiped out in North America by the 1950s, the parasite still kills over 400 000 people every year, 90% of whom live in sub-Saharan Africa. It has now developed resistance to many existing antimalarial drugs, meaning new treatments that work in different ways are urgently needed.
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
The researchers developed an array of compounds designed to prevent the parasites bursting out of blood cells, a vital replication step. One compound in particular was found to be very 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,” says Mike Blackman, lead author and group leader of the Malaria Biochemistry Laboratory at the Crick.
“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.”
Blocking the parasite’s emergence
The compound works by blocking an enzyme called SUB1, needed for them to burst out of cells. Current antimalarials kill the parasite within the cell, so the researchers hope this alternative drug action will overcome the resistance the parasite has acquired.
The compound can penetrate both the cell wall and the compartment within where the parasites reside.
The researchers are further refining the compound making it smaller and more potent. Further tests are needed before it can be trialled in humans.
Study author Chrislaine Withers-Martinez and researcher in the Malaria Biochemistry Laboratory, said: “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.”
Source: Francis Crick Institute
