通过鉴定关键靶标蛋白探究青蒿素抗疟机制  

Profiling the Antimalarial Mechanism of Artemisinin by Identifying Crucial Target Proteins

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

机构地区：[1]State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs,Artemisinin Research Center,and Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China [2]Pharmaceutical College,Henan University,Kaifeng 475004,China [3]Shandong Academy of Chinese Medicine,Jinan 250014,China [4]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

出　　处：《Engineering》2023年第12期86-97,共12页工程（英文）

基　　金：supported by grants from the National Key Research and Development Program of China(2020YFA0908000 and 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,and 82173914);the China Academy of Chinese Medical Sciences(CACMS)Innovation Fund(CI2021A05104 and 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,and ZZ15-ND-10);the Introduce Innovative Team Projects of Jinan(202228029)。

摘　　要：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.

关 键 词：ARTEMISININ ANTIMALARIA Target identification MS-CETSA TRANSCRIPTOMICS 

分 类 号：R285[医药卫生—中药学]