Cited by 1,852SARS-CoV-2 and COVID-19 ResearchAnimal Virus Infections StudiesCOVID-19 Clinical Research Studies

A Multibasic Cleavage Site in the Spike Protein of SARS-CoV-2 Is Essential for Infection of Human Lung Cells

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Hoffmann, Markus, Kleine-Weber, Hannah, Pöhlmann, Stefan·2020·Molecular Cell

Abstract

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.

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Crossref · 10.1016/j.molcel.2020.04.022

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  • The S protein is cleaved into S1 and S2 subunits during viral infection by the Furin enzyme and TMPRSS2.

    “The S protein is cleaved into S1 and S2 subunits during viral infection by the Furin enzyme and transmembrane serine protease 2 (TMPRSS2).231,232”

    From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [231]

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Authors
Hoffmann, M., Kleine-Weber, H., & Pöhlmann, S.
Affiliations
German Primate Center (DE)
Corresponding author
  • Hoffmann, Markus
  • Pöhlmann, Stefan
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2020-05
Volume
78
Issue
4
Pages
779-784.e5
ISSN
1097-2765 (ISSN-L)
OpenAlex
W3017302293
Cited by
1,852
References
52
Citations by year
2026: 60 · 2025: 116 · 2024: 182 · 2023: 228 · 2022: 396 · 2021: 542 · 2020: 327
FWCI
48.83
Type
journal article
Language
en
Open access
Locations
  • Molecular Cell (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Bundesministerium für Bildung und Forschung (01KI1723D)
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Keywords
SARS-CoV-2, spike protein, S1/S2 cleavage site, furin, proteolytic cleavage, cell-cell fusion, viral entry, human lung cells, viral variants, virulence, therapeutic target
MeSH terms
Betacoronavirus, COVID-19, SARS-CoV-2, Animals, Cell Line, Chlorocebus aethiops, Humans, Lung, Pneumonia, Viral, Serine Endopeptidases, Vero Cells, Coronavirus Infections, Furin, Virus Attachment, Pandemics, Spike Glycoprotein, Coronavirus

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