ArticlePLoS pathogens2021
Furin cleavage of SARS-CoV-2 Spike promotes but is not essential for infection and cell-cell fusion.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 236 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
236 citing papers in PubMed, 349 citations in OpenAlex.
- The conserved QTQTX motif in the SARS-CoV-2 spike protein is dispensable for cleavage and lung cell entry of the emerging variant BA.3.2.Journal of virology · 2026Article
- PD-L1 expression in tissues of cats with naturally occurring feline infectious peritonitis.Virology · 2026Article
- A divergent betacoronavirus with a functional furin cleavage site in South American bats.Nature communications · 2026Article
- Structural dynamics and allosteric communication of a SARS-like bat coronavirus spike glycoprotein.Biophysical journal · 2026Article
- Disruption of the S1/S2 multibasic cleavage site attenuates infectious bronchitis virus, while S2' partially restores viral virulence and expands tissue tropism.Journal of virology · 2026Article
- Hepatocyte growth factor activator inhibitor-2 rapidly inactivates airway-expressed human type II transmembrane serine proteases.The Journal of biological chemistry · 2026Article
- Viral syncytia evolve to resist interferon.Nature communications · 2026Article
- miR-29a and miR-15b Modulate SARS-CoV-2 Beta and Omicron Infection in Human Lung Epithelial Cells.International journal of molecular sciences · 2026Article
- Lock out: targeting TMPRSS2 to block influenza and coronaviruses.Journal of virology · 2026Review
- Furin as a Novel Pan-Viral Therapeutic Target: Implications for Dengue and SARS-CoV-2.Viruses · 2026Review
- Clade C MERS-CoV camel strains vary in protease utilization during viral entry.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Conformational dynamics of SARS-CoV-2 spike on a membrane reveals the allosteric effects of furin cleavage and the D614G mutation.Science advances · 2026Article
- Article
- K5 polysaccharides inhibit SARS-CoV-2 infection by preventing spike-proteolytic priming.Npj viruses · 2026Article
- Mathematical Modeling of Cell-Cell Fusion Assays to Characterize Virus-Mediated Cell Fusion.Advances in experimental medicine and biology · 2026Review
- Efficient production of fully active, SARS-CoV-2-priming, wildtype TMPRSS2 ectodomain via co-expression of HAI-2 allows for both auto- and cross-activation mechanisms.The Biochemical journal · 2025Article
- Effect of the S2' site cleavage on SARS-CoV-2 spike.Nature communications · 2025Article
- Perspective Overview of Changing Population Immunity to COVID-19 in the Context of Infection, Vaccination, and Emerging SARS-CoV-2 Variants.Pathogens (Basel, Switzerland) · 2025Review
- Clade C MERS-CoV camel strains vary in protease utilization during viral entry.bioRxiv : the preprint server for biology · 2025Article
- Nasal mucus-derived KLK13 restricts SARS-CoV-2 infection via proteolytic cleavage of spike.mBio · 2025Article
176 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infects cells by binding to the host cell receptor ACE2 and undergoing virus-host membrane fusion. Fusion is triggered by the protease TMPRSS2, which processes the viral Spike (S) protein to reveal the fusion peptide. SARS-CoV-2 has evolved a multibasic site at the S1-S2 boundary, which is thought to be cleaved by furin in order to prime S protein for TMPRSS2 processing. Here we show that CRISPR-Cas9 knockout of furin reduces, but does not prevent, the production of infectious SARS-CoV-2 virus. Comparing S processing in furin knockout cells to multibasic site mutants reveals that while loss of furin substantially reduces S1-S2 cleavage it does not prevent it. SARS-CoV-2 S protein also mediates cell-cell fusion, potentially allowing virus to spread virion-independently. We show that loss of furin in either donor or acceptor cells reduces, but does not prevent, TMPRSS2-dependent cell-cell fusion, unlike mutation of the multibasic site that completely prevents syncytia formation. Our results show that while furin promotes both SARS-CoV-2 infectivity and cell-cell spread it is not essential, suggesting furin inhibitors may reduce but not abolish viral spread.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.