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10.1016/j.celrep.2020.108254

http://scihub22266oqcxt.onion/10.1016/j.celrep.2020.108254
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suck abstract from ncbi


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pmid33007239      Cell+Rep 2020 ; 33 (2): 108254
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  • Furin Inhibitors Block SARS-CoV-2 Spike Protein Cleavage to Suppress Virus Production and Cytopathic Effects #MMPMID33007239
  • Cheng YW; Chao TL; Li CL; Chiu MF; Kao HC; Wang SH; Pang YH; Lin CH; Tsai YM; Lee WH; Tao MH; Ho TC; Wu PY; Jang LT; Chen PJ; Chang SY; Yeh SH
  • Cell Rep 2020[Oct]; 33 (2): 108254 PMID33007239show ga
  • 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.
  • |*Virus Replication[MESH]
  • |Amino Acid Chloromethyl Ketones/*pharmacology[MESH]
  • |Animals[MESH]
  • |Antiviral Agents/*pharmacology[MESH]
  • |Betacoronavirus/drug effects/metabolism/physiology[MESH]
  • |Chlorocebus aethiops[MESH]
  • |Fluoresceins/*pharmacology[MESH]
  • |Furin/*antagonists & inhibitors[MESH]
  • |Humans[MESH]
  • |Protease Inhibitors/*pharmacology[MESH]
  • |Proteolysis[MESH]
  • |SARS-CoV-2[MESH]
  • |Spike Glycoprotein, Coronavirus/*metabolism[MESH]


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