Profiling the Antimalarial Mechanism of Artemisinin by Identifying Crucial Target Proteins

Peng Gao, Jianyou Wang, Jiayun Chen, Liwei Gu, Chen Wang, Liting Xu, Yin Kwan Wong, Huimin Zhang, Chengchao Xu, Lingyun Dai, Jigang Wang

Engineering ›› 2023, Vol. 31 ›› Issue (12) : 86-97.

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Engineering ›› 2023, Vol. 31 ›› Issue (12) : 86-97. DOI: 10.1016/j.eng.2023.06.001
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Profiling the Antimalarial Mechanism of Artemisinin by Identifying Crucial Target Proteins

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Abstract

The widespread use of artemisinin (ART) and its derivatives has significantly reduced the global burden of malaria; however, malaria still poses a serious threat to global health. Although significant progress has been achieved in elucidating the antimalarial mechanisms of ART, the most crucial target proteins and pathways of ART remain unknown. Knowledge on the exact antimalarial mechanisms of ART is urgently needed, as signs of emerging ART resistance have been observed in some regions of the world. Here, we used a combined strategy involving mass spectrometry-coupled cellular thermal shift assay (MS-CETSA) and transcriptomics profiling to identify a group of putative antimalarial targets of ART. We then conducted a series of validation experiments on five prospective protein targets, demonstrating that ART may function against malaria parasites by interfering with redox homeostasis, lipid metabolism, and protein synthesis processes. Taken together, this study provides fresh perspectives on the antimalarial mechanisms of ART and identifies several crucial proteins involved in parasite survival that can be targeted to combat malaria.

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Artemisinin / Antimalaria / Target identification / MS-CETSA / Transcriptomics

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Peng Gao, Jianyou Wang, Jiayun Chen, Liwei Gu, Chen Wang, Liting Xu, Yin Kwan Wong, Huimin Zhang, Chengchao Xu, Lingyun Dai, Jigang Wang. Profiling the Antimalarial Mechanism of Artemisinin by Identifying Crucial Target Proteins. Engineering, 2023, 31(12): 86‒97 https://doi.org/10.1016/j.eng.2023.06.001

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Funding
the National Key Research and Development Program of China(2020YFA0908000, 2022YFC2303600); the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-C-202002); the National Natural Science Foundation of China(82141001, 82274182, 82074098, 82003814, 82173914); the China Academy of Chinese Medical Sciences (CACMS) Innovation Fund(CI2021A05104, CI2021A05101); the Distinguished Expert Project of Sichuan Province Tianfu Scholar(CW202002); the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(CI2021B014); the China Postdoctoral Science Foundation(2022M721541); the Establishment of Sino-Austria “Belt and Road” Joint Laboratory on Traditional Chinese Medicine for Severe Infectious Diseases and Joint Research(2020YFE0205100); the Excellent Scientific and Technological Innovation Training Program of Shenzhen(RCYX20210706092040048); the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ14-YQ-051, ZZ14-YQ-052, ZZ14-FL-002, ZZ14-YQ-050, ZZ14-ND-010, ZZ15-ND-10); the Introduce Innovative Team Projects of Jinan(202228029)
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