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DOI10.1016/j.scib.2020.12.005
Protoporphyrin IX and verteporfin potently inhibit SARS-CoV-2 infection in vitro and in a mouse model expressing human ACE2
Gu C.; Wu Y.; Guo H.; Zhu Y.; Xu W.; Wang Y.; Zhou Y.; Sun Z.; Cai X.; Li Y.; Liu J.; Huang Z.; Yuan Z.; Zhang R.; Deng Q.; Qu D.; Xie Y.
发表日期2020
ISSN20959273
英文摘要The SARS-CoV-2 infection is spreading rapidly worldwide. Efficacious antiviral therapeutics against SARS-CoV-2 is urgently needed. Here, we discovered that protoporphyrin IX (PpIX) and verteporfin, two Food and Drug Administration (FDA)-approved drugs, completely inhibited the cytopathic effect produced by SARS-CoV-2 infection at 1.25 µmol/L and 0.31 µmol/L, respectively, and their EC50 values of reduction of viral RNA were at nanomolar concentrations. The selectivity indices of PpIX and verteporfin were 952.74 and 368.93, respectively, suggesting a broad margin of safety. Importantly, PpIX and verteporfin prevented SARS-CoV-2 infection in mice adenovirally transduced with human angiotensin-converting enzyme 2 (ACE2). The compounds, sharing a porphyrin ring structure, were shown to bind viral receptor ACE2 and interfere with the interaction between ACE2 and the receptor-binding domain of viral S protein. Our study suggests that PpIX and verteporfin are potent antiviral agents against SARS-CoV-2 infection and sheds new light on developing novel chemoprophylaxis and chemotherapy against SARS-CoV-2. © 2020 Science China Press
关键词ACE2Protoporphyrin IXSARS-CoV-2Verteporfin
英文关键词Antiviral agents; Chemotherapy; Mammals; Angiotensin converting enzyme 2; Cytopathic effect; Food and Drug Administration; Margin of safety; Nanomolar concentration; Protoporphyrin IX; Receptor-binding domains; Selectivity index; Diseases
语种英语
来源期刊Science Bulletin
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/207042
作者单位Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai Medical College, Fudan University, Shanghai, 200032, China; BSL-3 Laboratory of Fudan University, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China; CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China; Children's Hospital, Shanghai Medical College, Fudan University, Shanghai, 201102, China
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GB/T 7714
Gu C.,Wu Y.,Guo H.,et al. Protoporphyrin IX and verteporfin potently inhibit SARS-CoV-2 infection in vitro and in a mouse model expressing human ACE2[J],2020.
APA Gu C..,Wu Y..,Guo H..,Zhu Y..,Xu W..,...&Xie Y..(2020).Protoporphyrin IX and verteporfin potently inhibit SARS-CoV-2 infection in vitro and in a mouse model expressing human ACE2.Science Bulletin.
MLA Gu C.,et al."Protoporphyrin IX and verteporfin potently inhibit SARS-CoV-2 infection in vitro and in a mouse model expressing human ACE2".Science Bulletin (2020).
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