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Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus
Wang et al., Phytomedicine, doi:10.1016/j.phymed.2020.153333 (In Vitro)
Wang et al., Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus, Phytomedicine, doi:10.1016/j.phymed.2020.153333 (In Vitro)
Sep 2020   Source   PDF  
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In Vitro study providing novel insights into the molecular mechanism of CQ/HCQ treatment, showing that CQ and HCQ both inhibit the entrance of 2019-nCoV into cells by blocking the binding of the virus with ACE2.
14 In Vitro studies support the efficacy of HCQ [Andreani, Clementi, Dang, Delandre, Faísca, Hoffmann, Liu, Ou, Purwati, Sheaff, Wang, Wang (B), Yao, Yuan].
Wang et al., 2 Sep 2020, peer-reviewed, 34 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
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Abstract: Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Phytomedicine 79 (2020) 153333 Contents lists available at ScienceDirect Phytomedicine journal homepage: Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus T Nan Wanga,b,1, Shengli Hana,b,1, Rui Liua,b,1, Liesu Mengc,d,1, Huaizhen Hea,b,1, Yongjing Zhanga,b,1, Cheng Wanga,b, Yanni Lva,b, Jue Wanga,b, Xiaowei Lic,d, Yuanyuan Dinga,b, Jia Fua,b, Yajing Houa,b, Wen Lua,b, Weina Maa,b, Yingzhuan Zhana,b, Bingling Daia,b, Jie Zhanga,b, Xiaoyan Pana,b, Shiling Hua,b, Jiapan Gaoa,b, Qianqian Jiaa,b, Liyang Zhanga,b, Shuai Gea,b, Saisai Wanga,b, Peida Lianga,b, Tian Hua,b, Jiayu Lua,b, Xiangjun Wanga,b, Huaxin Zhoua,b, ⁎ ⁎ Wenjing Taa,b, Yuejin Wanga,b, Shemin Luc,d, , Langchong Hea,b, a School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shannxi, 710061, China Institute of Vascular Materia Medica, Xi'an Jiaotong University, Xi'an, Shaanxi,710116, China c Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, West Yanta Road No.76, Xi'an, Shaanxi 710061, China d The Second Affiliated Hospital of Xi'an Jiaotong University (Xibei Hospital), Xi'an, Shaanxi 710004, China b ARTICLE INFO ABSTRACT Keywords: Chloroquine Hydroxychloroquine 2019-nCoV ACE2 Background: The 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. Purpose: The objective of this study is to investigate whether CQ and HCQ could be ACE2 blockers and used to inhibit 2019-nCoV virus infection. Methods: In 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. Results: Results 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. Conclusions: CQ and HCQ both inhibit the entrance 2019-nCoV into cells by blocking the..
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