Malaria breakthrough promises better drugs

TWO BIOCHEMISTS at the Indian Institute of Science say chloroquine -- the primary drug used to combat malaria -- works against the malarial parasite, Plasmodium falciparum, by inhibiting protein synthesis.

"This knowledge will help us understand how the parasite builds up resistance to the drug and it will also open up a whole new area of rational drug design," says Govindarajan Padmanabhan who made the discovery along with his colleague Namita Surolia.

The two found the malarial parasite lodges itself in the red blood cells of the human host and feeds on haemoglobin -- a red, oxygen-carrying substance containing iron -- to produce its own proteins. The parasite is known to gobble up as much as 75 per cent of the haemoglobin found in red blood cells. In the process, it detoxifies haemoglobin's iron-containing portion called heme, and stores it within itself as an inert complex.

Ironically, as the two scientists discovered, the parasite also requires heme to produce its own proteins and enzymes because it is unable to use human heme and so is forced to produce its own. Chloroquine, the scientists say, combines with heme and inhibits protein synthesis in the parasite by as much as 80 per cent.

The scientists have also isolated the enzymes in the parasite that are involved in synthesising heme. Blocking one or more of these enzymes, they suggest, could be a possible therapeutic target for the future. Though this work opens up exciting possibilities for drug design, Padmanabhan warns: "If they intend to interfere with heme synthesis in Plasmodium, scientists must be very sure of what they do for heme is essential for the parasite's human host as well."