3D malaria image important to antimalarial drugs
"Plasmepsin V acts like a bus conductor, giving each protein that needs to leave the parasite a stamp of approval and a ticket to the correct destination," Professor Alan Cowman, lead researcher, said. "It is an important target given its critical role in the survival of malaria parasites and expression at all stages of its lifecycle."
The scientists from Melbourne’s Walter and Eliza Hall Institute have created WEHI-842.
"There has been significant interest in solving the structure of plasmepsin V, which has been a very tricky venture given the nature of the protein,” Professor Cowman said. “Using the potent drug WEHI-842, we were able to stabilise the protein sufficiently to detail its molecular structure, which will be critical in developing this new class of antimalarial drugs."
This is a new drug that blogs plasmepsin V, a malaria parasite protein, and this blockage effectively kills the parasite.
"WEHI-842 is a very effective agent in preventing the growth and survival of Plasmodium falciparum," Dr. Justin Boddey, a member of the scientific team, said. "Plasmodium falciparum is the most deadly form of malaria parasite, causing most of the 800,000 deaths from malaria each year. Plasmodium vivax is also particularly insidious because it can hide in the body for long periods of time without symptoms, causing disease relapses much later."
This is the first step in creating desperately needed innovative drugs for preventing and treating malaria.
"WEHI-842 is able to strongly bind to and disrupt the function of plasmepsin V, preventing the release of proteins that are critical for shaping the parasite's environment and, effectively, killing it," Boddey said. "Plasmepsin V is expressed by the different shapeshifters across the lifecycle so we should be able to kill these different forms as well."
The 3D image of the protein’s molecular structure was crucial to creating this new drug.
"The malaria parasite hides exceptionally well in the liver and red blood cells, with four walls between the bloodstream and the protein we are targeting," Boddey said. "We are now collaborating with a pharmaceutical company to identify drugs that act in the same way as WEHI-842, but are able to find a way through these four walls to access the parasite hidden deep inside the red blood cell."