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Development of Artemisinin booster compounds to overcome artemisinin resistance

Principal Investigator :  Thanat Chookajorn, Genomics & Evolutionary Medicine

Project Status : On-going

 

Project Summary

Artemisinin has been the gold standard for malaria treatment since its discovery.  The adoption of Artemisinin combination therapies (ACT) has been a major contributor to the recent decline in malaria mortality. What separated artemisinin from other antimalaria agents was its ability to kill malaria parasites at all stages of the life cycle. However, there has been a worrying trend in which during the early stages of the malaria parasites life cycle, the ring stage, the parasite is showing reduced sensitivity to artemisinin. This causes an issue as artemisinin has an incredibly short half-life, approximately 16 minutes in humans. This decreased sensitivity allows the parasite to survive the drug treatment. As it currently stands Artemisinin can still cure malaria infections but parasites exhibiting reduced artemisinin sensitivity have been spreading in Thailand, Cambodia, and Myanmar. Recent molecular studies have shown the resistance is spreading further west, through north India which is seen as the gateway to Africa. As such an effective strategy for fighting malarial parasites with reduced sensitivity to Artemisinin must be developed.  The Chookajorn laboratory in collaboration with a team from GlaxoSmithKline is using a screening approach to find compounds that can be used in combination with Artemisinin to restore its effectiveness during the ring stage of the malaria life cycle.  The project has found protease inhibitors and thiourea like compounds to boost the efficacy of artemisinin in p. vivax that shown artemisinin resistance.  The next steps include further compound optimization where they will attempt to further improve and enhance the promising drug candidates. If successful, the study can then move onto a pre-clinical stage where the efficacy will be tested in vivo.