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Artemisinin’s exact biochemical targets are still being fully elucidated, but research has identified several likely protein targets and cellular pathways that are disrupted by the drug’s action. Here’s what is currently known: 

Biochemical Targets of Artemisinin

Once activated by iron (from heme), artemisinin generates free radicals that bind to and alkylate multiple parasite proteins. These are the main biochemical targets:

1. PfATP6 (SERCA-like Calcium ATPase)

• A sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase ortholog in P. falciparum.

• Artemisinin was proposed to inhibit PfATP6, disturbing calcium homeostasis, which is essential for parasite survival and development.

• Note: Some later studies questioned this as the primary target, but it’s still considered important.

2. Parasite Proteins Rich in Iron or Heme Groups

• Hemoglobin-digesting enzymes (like plasmepsins and falcipains) generate heme for artemisinin activation.

• The resulting free radicals alkylate these and other nearby proteins, leading to dysfunction and cell death.

3. Mitochondrial and Redox Pathways

• Artemisinin damages mitochondrial membranes and disrupts electron transport and redox balance.

• This causes oxidative stress, a major mechanism in parasite killing.

4. Proteins Involved in Protein Folding and Translation

• Mass spectrometry has identified artemisinin binding to:

• Translational initiation factors

• Heat shock proteins (e.g., PfHsp70, PfHsp90)

• Ribosomal proteins

• These affect protein synthesis and stress responses.

5. PfKelch13 (Not a Direct Target, But Related to Resistance)

• PfKelch13 is not the target of artemisinin itself, but mutations here (like C580Y) are strongly associated with artemisinin resistance.

• The protein is thought to be involved in endocytosis and ubiquitin pathways, and its mutation slows parasite clearance by blunting damage response.

Summary

Artemisinin doesn’t have one single target—it’s a multi-target drug. Its activated form binds covalently to several critical parasite proteins, especially those in calcium regulation, redox balance, protein folding, and metabolism, leading to rapid parasite death.

References

1. Eckstein-Ludwig, U., Webb, R. J., Van Goethem, I. D., East, J. M., Lee, A. G., Kimura, M., ... & Krishna, S. (2003). Artemisinins target the SERCA of Plasmodium falciparum. Nature, 424(6951), 957–961. https://doi.org/10.1038/nature01813
   
   

2. Meshnick, S. R. (2002). Artemisinin: mechanisms of action, resistance and toxicity. International journal for parasitology, 32(13), 1655-1660.
   
   

3. Wang, J., Zhang, C. J., Chia, W. N., Loh, C. C., Li, Z., Lee, Y. M., ... & Lin, Q. (2015). Haem-activated promiscuous targeting of artemisinin in Plasmodium falciparum. Nature communications, 6(1), 10111.
   
   

4. Ismail, H. M., Barton, V., Phanchana, M., Charoensutthivarakul, S., Wong, M. H., Hemingway, J., ... & Ward, S. A. (2016). Artemisinin activity-based probes identify multiple molecular targets within the asexual stage of the malaria parasites Plasmodium falciparum 3D7. Proceedings of the National Academy of Sciences, 113(8), 2080-2085.
   
   

5. Ariey, F., Witkowski, B., Amaratunga, C., Beghain, J., Langlois, A. C., Khim, N., ... & Menard, D. (2014). A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature, 505(7481), 50–55. https://doi.org/10.1038/nature12876

May 30, 2025 Tags : #MalariaResistance #MalariaTreatment #GhanaHealth #DrugResistance #Artemisinin #SPResistance #MalariaResearch #PublicHealth #InfectiousDiseases #MalariaAwareness #Genetics #HealthEducation

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