The malaria group at the University of Hyderabad (UoH) lead by Professor Mrinal Kanti Bhattacharyya has identified a small chemical inhibitor of DNA recombinase enzyme from Plasmodium that blocks the repair of parasite genome and hence curb malaria. This work is published in a recent issue of the Journal of Biological Chemistry (JBC). The idea of targetingPlasmodium homologous recombination (HR) machinery stems from an earlier report from the same group that unrepaired DNA double strand breaks (DSB) leads to the death of unicellular Plasmodium, where HR is the main DSB repair pathway.

This inhibitor (B02) is equally effective against drug sensitive and multi-drug resistant malaria strains. Most importantly it potentiates the action of two first-line malaria drugs Artemisinin (ART) and Chloroquine (CQ). Currently, ART is the WHO prescribed last resort to treat cerebral malaria. Thus, the emergence of ART resistant malaria parasites from different part of the world cries for the discovery of newer antimalarial compounds. Hence, increasing the effectiveness of ART through ART-combination therapy is the need of the hour. To this end this is a very timely discovery from the Bhattacharyya laboratory that demonstrated 15 fold more effectiveness of their combination compared to the ART alone. Such synergism was also observed for CQ, where CQ action was potentiated by 8 fold.

This work was carried at the School of Life Sciences by Prof. Mrinal Kanti Bhattacharyya, Pratap Vydyam, Dibyendu Dutta and Niranjan Suthram from the Department of Biochemistry in collaboration with Dr. Sunanda Bhattacharyya from the Department of Biotechnology and Bioinformatics.

This compound selectively blocks the repair of Plasmodium genome compared to the genomes of mouse or human. This could be a new hope for malaria treatment and is currently awaiting animal testing.

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