Background:

• Researchers from New Delhi have, for the first time, deciphered a multiprotein complex that is involved in the invasion of the red blood cells (RBCs) by Plasmodium falciparum malaria parasites.
• They have also identified a peptide molecule that can effectively prevent the interaction between malaria parasites and receptors found on RBCs thereby preventing the parasites from invading the RBCs and causing the disease.

More Details:

• During infection with Plasmodium species, the parasite invades RBCs and replicates inside them. It is during the blood stage of infection that malaria disease occurs.
• P. falciparum parasites  are known to quickly develop resistance against drugs through mutations.
• An immunosuppressive drug (cyclosporine A) that binds to cyclophilin B receptors on RBCs is effective in killing malaria parasites. “But in mice model it has been shown that the drug has adverse effects as it also kills RBCs.
• Using the drug in two different experiments we confirmed that cyclophilin B receptors were involved in the invasion process.
• There are two main receptors on RBCs and two parasite proteins which form a four-protein complex.
• By interrupting the binding of the parasite protein with RBCs at one of the receptors the whole protein complex falls apart. It is like a number lock with a four-digit combination. Interrupting any one of the steps will prevent the parasite invasion of RBCs.
• Having deciphered the mechanism of parasite entry, the team is now working to reduce the dosage to use the peptide as a drug. “We can either modify the cyclosporine A drug to make it less toxic and use it for preventing malaria or use the peptide as an inhibitor. It is easier to take the drug than the peptide to clinical testing by making necessary modifications.

Source:TH