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
Affiliations
Peng Gao
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
Jianyou Wang
Pharmaceutical College, Henan University, Kaifeng 475004, China
Jiayun Chen
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
Liwei Gu
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
Chen Wang
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
Liting Xu
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
Yin Kwan Wong
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
Huimin Zhang
Shandong Academy of Chinese Medicine, Jinan 250014, China
Chengchao Xu
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; Department of Infectious Disease, Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital & the First Affiliated Hospital of Southern University of Science and Technology, Shenzhen 518020, China; Corresponding authors.
Lingyun Dai
Department of Infectious Disease, Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital & the First Affiliated Hospital of Southern University of Science and Technology, Shenzhen 518020, China; Corresponding authors.
Jigang Wang
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; Pharmaceutical College, Henan University, Kaifeng 475004, China; Shandong Academy of Chinese Medicine, Jinan 250014, China; Department of Infectious Disease, Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital & the First Affiliated Hospital of Southern University of Science and Technology, Shenzhen 518020, China; Corresponding authors.
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.
