User login
infecting a red blood cell
Photo courtesy of St. Jude
Children’s Research Hospital
Researchers say they have gained a better understanding of how the antimalarial drug artemisinin kills the Plasmodium falciparum parasite.
A chemical proteomics analysis revealed more than 120 protein targets of artemisinin and the mechanism that activates its killing effect.
Given the emergence of artemisinin resistance, the team believes their findings could aid the design of new treatments against drug-resistant parasites.
They reported the findings in Nature Communications.
Previously, only 2 targets of artemisinin had been identified, and their correlation with the parasite-killing effect of the drug had been questioned.
Lin Qingsong, PhD, of the National University of Singapore, and his colleagues identified 124 protein targets of artemisinin in P falciparum. Many of these newly identified protein targets are involved in essential biological processes in the parasite, thus explaining artemisinin’s potent killing effect.
The research suggests that, through its promiscuous targeting mechanism, artemisinin targets the blood-eating nature of the malaria parasite, binding to a broad spectrum of targets simultaneously and fatally disrupting the biochemistry of the parasite.
The study also showed that the main activator of artemisinin is heme, an iron-containing compound that is either biosynthesized by the parasite at its early developmental ring stage or derived from hemoglobin digestion in the later stages.
The drug activation level was found to be much lower in ring-stage parasites, given that artemisinin activation requires heme, which is of much lower abundance and is biosynthesized by the parasite.
In comparison, during the late stages of its life cycle, the parasite actively digests the hemoglobin in infected blood cells as its primary energy source. This releases large amounts of heme, and the drug is able to specifically respond to parasite-infected cells and effectively attack the disease-causing parasites.
“The current findings not only provide a more complete picture of how artemisinin and its derivatives work but also suggest new ways of using the drug,” Dr Lin said. “For instance, to improve drug activation at ring stage, we can explore enhancing the level of heme biosynthesis in the parasite.”
“By understanding that hemoglobin digestion releases huge amounts of heme, which brings about the effective killing mechanism in the later stages, we can also consider prolonging the treatment time to ensure that the drug can effectively kill the parasite through multiple cycles.”
In addition, the researchers are planning to develop novel artemisinin analogues with more specific targeting properties. 
infecting a red blood cell
Photo courtesy of St. Jude
Children’s Research Hospital
Researchers say they have gained a better understanding of how the antimalarial drug artemisinin kills the Plasmodium falciparum parasite.
A chemical proteomics analysis revealed more than 120 protein targets of artemisinin and the mechanism that activates its killing effect.
Given the emergence of artemisinin resistance, the team believes their findings could aid the design of new treatments against drug-resistant parasites.
They reported the findings in Nature Communications.
Previously, only 2 targets of artemisinin had been identified, and their correlation with the parasite-killing effect of the drug had been questioned.
Lin Qingsong, PhD, of the National University of Singapore, and his colleagues identified 124 protein targets of artemisinin in P falciparum. Many of these newly identified protein targets are involved in essential biological processes in the parasite, thus explaining artemisinin’s potent killing effect.
The research suggests that, through its promiscuous targeting mechanism, artemisinin targets the blood-eating nature of the malaria parasite, binding to a broad spectrum of targets simultaneously and fatally disrupting the biochemistry of the parasite.
The study also showed that the main activator of artemisinin is heme, an iron-containing compound that is either biosynthesized by the parasite at its early developmental ring stage or derived from hemoglobin digestion in the later stages.
The drug activation level was found to be much lower in ring-stage parasites, given that artemisinin activation requires heme, which is of much lower abundance and is biosynthesized by the parasite.
In comparison, during the late stages of its life cycle, the parasite actively digests the hemoglobin in infected blood cells as its primary energy source. This releases large amounts of heme, and the drug is able to specifically respond to parasite-infected cells and effectively attack the disease-causing parasites.
“The current findings not only provide a more complete picture of how artemisinin and its derivatives work but also suggest new ways of using the drug,” Dr Lin said. “For instance, to improve drug activation at ring stage, we can explore enhancing the level of heme biosynthesis in the parasite.”
“By understanding that hemoglobin digestion releases huge amounts of heme, which brings about the effective killing mechanism in the later stages, we can also consider prolonging the treatment time to ensure that the drug can effectively kill the parasite through multiple cycles.”
In addition, the researchers are planning to develop novel artemisinin analogues with more specific targeting properties.
infecting a red blood cell
Photo courtesy of St. Jude
Children’s Research Hospital
Researchers say they have gained a better understanding of how the antimalarial drug artemisinin kills the Plasmodium falciparum parasite.
A chemical proteomics analysis revealed more than 120 protein targets of artemisinin and the mechanism that activates its killing effect.
Given the emergence of artemisinin resistance, the team believes their findings could aid the design of new treatments against drug-resistant parasites.
They reported the findings in Nature Communications.
Previously, only 2 targets of artemisinin had been identified, and their correlation with the parasite-killing effect of the drug had been questioned.
Lin Qingsong, PhD, of the National University of Singapore, and his colleagues identified 124 protein targets of artemisinin in P falciparum. Many of these newly identified protein targets are involved in essential biological processes in the parasite, thus explaining artemisinin’s potent killing effect.
The research suggests that, through its promiscuous targeting mechanism, artemisinin targets the blood-eating nature of the malaria parasite, binding to a broad spectrum of targets simultaneously and fatally disrupting the biochemistry of the parasite.
The study also showed that the main activator of artemisinin is heme, an iron-containing compound that is either biosynthesized by the parasite at its early developmental ring stage or derived from hemoglobin digestion in the later stages.
The drug activation level was found to be much lower in ring-stage parasites, given that artemisinin activation requires heme, which is of much lower abundance and is biosynthesized by the parasite.
In comparison, during the late stages of its life cycle, the parasite actively digests the hemoglobin in infected blood cells as its primary energy source. This releases large amounts of heme, and the drug is able to specifically respond to parasite-infected cells and effectively attack the disease-causing parasites.
“The current findings not only provide a more complete picture of how artemisinin and its derivatives work but also suggest new ways of using the drug,” Dr Lin said. “For instance, to improve drug activation at ring stage, we can explore enhancing the level of heme biosynthesis in the parasite.”
“By understanding that hemoglobin digestion releases huge amounts of heme, which brings about the effective killing mechanism in the later stages, we can also consider prolonging the treatment time to ensure that the drug can effectively kill the parasite through multiple cycles.”
In addition, the researchers are planning to develop novel artemisinin analogues with more specific targeting properties.