Genomic Analysis Yields New Malaria Drug Candidates

High-throughput chemical screening and genome-wide association analysis have been used to identify potential new drug candidates for the treatment of malaria.

Malaria remains a devastating disease largely because of widespread drug resistance. Therefore, the discovery of new drugs and development of a better understanding of the mechanisms of drug action and resistance are essential for fulfilling the promise of eradicating malaria.

Towards this end, investigators at the [US] National Institutes of Health (Bethesda, MD, USA) used advanced high-throughput chemical screening techniques to evaluate more than 2,800 chemical compounds for activity against 61 genetically diverse strains of laboratory-grown malaria parasites.

They reported in the August 5, 2011, issue of the journal Science that they had found 32 compounds that were highly effective at killing at least 45 of the 61 strains. Ten of these compounds had not previously been reported to have antimalarial action, and seven were more active at lower concentrations than artemisinin, a widely used malaria drug. All the screened compounds have already been registered as safe or approved for use in humans or animals, although not necessarily for use against malaria.

Genome-wide association analysis revealed that the same three genes that confer resistance to currently used malaria drugs were associated with resistance to many of the newly screened compounds. This finding suggests that the malaria parasite has a limited number of ways to develop resistance following exposure to drugs, and that suitable drug combinations could be devised to target activity of all three resistance genes simultaneously.

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National Institutes of Health