Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus
Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus
Abstract BackgroundThe novel coronavirus disease (2019-nCoV) has been affecting global health since the end of 2019 and there is no sign that the epidemic is abating. The major issue for controlling the infectious is lacking efficient prevention and therapeutic approaches. Chloroquine (CQ) and Hydroxychloroquine (HCQ) have been reported to treat the disease, but the underlying mechanism remains controversial. PurposeThe objective of this study is to investigate whether CQ and HCQ could be ACE2 blockers and used to inhibit 2019-nCoV virus infection. MethodsIn our study, we used CCK-8 staining, flow cytometry and immunofluorescent staining to evaluate the toxicity and autophagy of CQ and HCQ, respectively, on ACE2 high-expressing HEK293T cells (ACE2h cells). We further analyzed the binding character of CQ and HCQ to ACE2 by molecular docking and surface plasmon resonance (SPR) assays, 2019-nCoV spike pseudotyped virus was also used to observe the viropexis effect of CQ and HCQ in ACE2h cells. ResultsResults showed that HCQ is slightly more toxic to ACE2h cells than CQ. Both CQ and HCQ could bind to ACE2 with KD =(7.31±0.62)e?7 M and (4.82±0.87)e?7 M, respectively. They exhibit equivalent suppression effect for the entrance of 2019-nCoV spike pseudotyped virus into ACE2h cells. ConclusionsCQ and HCQ both inhibit the entrance 2019-nCoV into cells by blocking the binding of the virus with ACE2. Our findings provide novel insights into the molecular mechanism of CQ and HCQ treatment effect on virus infection.
Hu Tian、Jia Qianqian、Zhang Liyang、Wang Saisai、Meng Liesu、Zhou Huaxin、Ta Wenjing、Wang Yuejin、Wang Cheng、Lv Yanni、Li Xiaowei、Hou Yajing、Ma Weina、Dai Bingling、Pan Xiaoyan、Lu Shemin、He Huaizhen、Gao Jiapan、Wang Xiangjun、Liang Peida、Han Shengli、Zhan Yingzhuan、Fu Jia、Ding Yuanyuan、Zhang Jie、Ge Shuai、He Langchong、Lu Wen、Liu Rui、Zhang Yongjing、Wang Jue、Wang Nan、Hu Shiling、Lu Jiayu
School of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversityDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi?ˉan Jiaotong University Health Science Center||The Second Affiliated Hospital of Xi?ˉan Jiaotong University (Xibei Hospital)School of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversityDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi?ˉan Jiaotong University Health Science Center||The Second Affiliated Hospital of Xi?ˉan Jiaotong University (Xibei Hospital)School of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversityDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi?ˉan Jiaotong University Health Science Center||The Second Affiliated Hospital of Xi?ˉan Jiaotong University (Xibei Hospital)School of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong UniversitySchool of Pharmacy, Xi?ˉan Jiaotong University||Institute of Vascular Materia Medica, Xi?ˉan Jiaotong University
医药卫生理论医学研究方法药学
chloroquinehydroxychloroquine2019-nCoVACE2
Hu Tian,Jia Qianqian,Zhang Liyang,Wang Saisai,Meng Liesu,Zhou Huaxin,Ta Wenjing,Wang Yuejin,Wang Cheng,Lv Yanni,Li Xiaowei,Hou Yajing,Ma Weina,Dai Bingling,Pan Xiaoyan,Lu Shemin,He Huaizhen,Gao Jiapan,Wang Xiangjun,Liang Peida,Han Shengli,Zhan Yingzhuan,Fu Jia,Ding Yuanyuan,Zhang Jie,Ge Shuai,He Langchong,Lu Wen,Liu Rui,Zhang Yongjing,Wang Jue,Wang Nan,Hu Shiling,Lu Jiayu.Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus[EB/OL].(2025-03-28)[2025-05-13].https://www.biorxiv.org/content/10.1101/2020.06.22.164665.点此复制
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