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10.1016/j.molcel.2020.04.022

http://scihub22266oqcxt.onion/10.1016/j.molcel.2020.04.022
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32362314!7194065!32362314
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suck abstract from ncbi


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pmid32362314      Mol+Cell 2020 ; 78 (4): 779-784.e5
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  • A Multibasic Cleavage Site in the Spike Protein of SARS-CoV-2 Is Essential for Infection of Human Lung Cells #MMPMID32362314
  • Hoffmann M; Kleine-Weber H; Pohlmann S
  • Mol Cell 2020[May]; 78 (4): 779-784.e5 PMID32362314show ga
  • The pandemic coronavirus SARS-CoV-2 threatens public health worldwide. The viral spike protein mediates SARS-CoV-2 entry into host cells and harbors a S1/S2 cleavage site containing multiple arginine residues (multibasic) not found in closely related animal coronaviruses. However, the role of this multibasic cleavage site in SARS-CoV-2 infection is unknown. Here, we report that the cellular protease furin cleaves the spike protein at the S1/S2 site and that cleavage is essential for S-protein-mediated cell-cell fusion and entry into human lung cells. Moreover, optimizing the S1/S2 site increased cell-cell, but not virus-cell, fusion, suggesting that the corresponding viral variants might exhibit increased cell-cell spread and potentially altered virulence. Our results suggest that acquisition of a S1/S2 multibasic cleavage site was essential for SARS-CoV-2 infection of humans and identify furin as a potential target for therapeutic intervention.
  • |Animals[MESH]
  • |Betacoronavirus/*chemistry/physiology[MESH]
  • |COVID-19[MESH]
  • |Cell Line[MESH]
  • |Chlorocebus aethiops[MESH]
  • |Coronavirus Infections/*virology[MESH]
  • |Furin/chemistry/genetics/metabolism[MESH]
  • |Humans[MESH]
  • |Lung/metabolism/virology[MESH]
  • |Pandemics[MESH]
  • |Pneumonia, Viral/*virology[MESH]
  • |SARS-CoV-2[MESH]
  • |Serine Endopeptidases/metabolism[MESH]
  • |Spike Glycoprotein, Coronavirus/*chemistry/genetics/metabolism[MESH]
  • |Vero Cells[MESH]


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