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Furin Inhibitors Block SARS-CoV-2 Spike Protein Cleavage to Suppress Virus Production and Cytopathic Effects.
Cheng, Ya-Wen; Chao, Tai-Ling; Li, Chiao-Ling; Chiu, Mu-Fan; Kao, Han-Chieh; Wang, Sheng-Han; Pang, Yu-Hao; Lin, Chih-Hui; Tsai, Ya-Min; Lee, Wen-Hau; Tao, Mi-Hua; Ho, Tung-Ching; Wu, Ping-Yi; Jang, Li-Ting; Chen, Pei-Jer; Chang, Sui-Yuan; Yeh, Shiou-Hwei.
  • Cheng YW; Department of Microbiology, National Taiwan University College of Medicine, Taipei 100, Taiwan.
  • Chao TL; Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei 100, Taiwan.
  • Li CL; Department of Microbiology, National Taiwan University College of Medicine, Taipei 100, Taiwan.
  • Chiu MF; Department of Microbiology, National Taiwan University College of Medicine, Taipei 100, Taiwan.
  • Kao HC; Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei 100, Taiwan.
  • Wang SH; Hepatitis Research Center, National Taiwan University Hospital, Taipei 100, Taiwan.
  • Pang YH; Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei 100, Taiwan.
  • Lin CH; Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei 100, Taiwan.
  • Tsai YM; Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei 100, Taiwan.
  • Lee WH; Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei 100, Taiwan.
  • Tao MH; Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
  • Ho TC; Department of Microbiology, National Taiwan University College of Medicine, Taipei 100, Taiwan.
  • Wu PY; Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
  • Jang LT; Biomedical Resource Core at the First Core Labs, Branch Office of Research and Development, National Taiwan University College of Medicine, Taipei 100, Taiwan.
  • Chen PJ; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 100, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan; National Taiwan University Center for Genomic Medicine, National Taiwan University College of Medicin
  • Chang SY; Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei 100, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei 100, Taiwan. Electronic address: sychang@ntu.edu.tw.
  • Yeh SH; Department of Microbiology, National Taiwan University College of Medicine, Taipei 100, Taiwan; Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei 100, Taiwan; National Taiwan University Center for Genomic Medicine, National T
Cell Rep ; 33(2): 108254, 2020 10 13.
Article in English | MEDLINE | ID: covidwho-812312
ABSTRACT
Development of specific antiviral agents is an urgent unmet need for SARS-coronavirus 2 (SARS-CoV-2) infection. This study focuses on host proteases that proteolytically activate the SARS-CoV-2 spike protein, critical for its fusion after binding to angiotensin-converting enzyme 2 (ACE2), as antiviral targets. We first validate cleavage at a putative furin substrate motif at SARS-CoV-2 spikes by expressing it in VeroE6 cells and find prominent syncytium formation. Cleavage and the syncytium are abolished by treatment with the furin inhibitors decanoyl-RVKR-chloromethylketone (CMK) and naphthofluorescein, but not by the transmembrane protease serine 2 (TMPRSS2) inhibitor camostat. CMK and naphthofluorescein show antiviral effects on SARS-CoV-2-infected cells by decreasing virus production and cytopathic effects. Further analysis reveals that, similar to camostat, CMK blocks virus entry, but it further suppresses cleavage of spikes and the syncytium. Naphthofluorescein acts primarily by suppressing viral RNA transcription. Therefore, furin inhibitors may be promising antiviral agents for prevention and treatment of SARS-CoV-2 infection.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Protease Inhibitors / Virus Replication / Furin / Spike Glycoprotein, Coronavirus / Fluoresceins / Amino Acid Chloromethyl Ketones Type of study: Experimental Studies / Prognostic study Limits: Animals / Humans Language: English Journal: Cell Rep Year: 2020 Document Type: Article Affiliation country: J.celrep.2020.108254

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Protease Inhibitors / Virus Replication / Furin / Spike Glycoprotein, Coronavirus / Fluoresceins / Amino Acid Chloromethyl Ketones Type of study: Experimental Studies / Prognostic study Limits: Animals / Humans Language: English Journal: Cell Rep Year: 2020 Document Type: Article Affiliation country: J.celrep.2020.108254