ArticleNature microbiology2021
The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets.
Article in Nature microbiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 488 papers.
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Who cites it
488 citing papers in PubMed, 789 citations in OpenAlex.
- Article
- 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
- A divergent betacoronavirus with a functional furin cleavage site in South American bats.Nature communications · 2026Article
- Serum Escape Landscape of SARS-CoV-2 Omicron JN.1 and XEC RBD Under COVID-19 Vaccine Breakthrough Immunity in China.Microorganisms · 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
- Loss-of-function mutation in Omicron variants reduces spike protein expression and attenuates SARS-CoV-2 infection.Nature communications · 2026Article
- Peptides containing SARS-CoV-2 spike-protein residues are antagonists of α7 and α9α10 nAChRs and modulate interleukin-1β release from human monocytic THP-1 cells.The Journal of biological chemistry · 2026Article
- Viral syncytia evolve to resist interferon.Nature communications · 2026Article
- Lock out: targeting TMPRSS2 to block influenza and coronaviruses.Journal of virology · 2026Review
- Article
- Maturation-deficient chikungunya virus elicits protective immune responses in a murine challenge model.NPJ vaccines · 2026Article
- TMPRSS2-mediated coronavirus spike activation and inhibition.Nature structural & molecular biology · 2026Article
- Furin as a Novel Pan-Viral Therapeutic Target: Implications for Dengue and SARS-CoV-2.Viruses · 2026Review
- Genetic polymorphisms and expression of SARS-CoV-2 host entry genes associate with COVID-19 severity in an unvaccinated Moroccan cohort.BMC medical genomics · 2026Article
- 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
- Tea Polyphenols in the COVID-19 Era: Mechanistic Insights and Translational Challenges.Current issues in molecular biology · 2026Review
- COVID-19, the disease that changed the world.Medicine and pharmacy reports · 2026Review
- Accumulation of mutations in nsp4, E, and the S2 subunit underlies mammalian cell tropism expansion and virulence attenuation of avian coronavirus.PLoS pathogens · 2026Article
- Entry, replication and innate immunity evasion of BANAL-236, a SARS-CoV-2-related bat virus, in Rhinolophus and human cells.PLoS pathogens · 2026Article
428 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 4 institutions in 1 country.
Funding
Abstract
SARS-CoV-2 entry requires sequential cleavage of the spike glycoprotein at the S1/S2 and the S2' cleavage sites to mediate membrane fusion. SARS-CoV-2 has a polybasic insertion (PRRAR) at the S1/S2 cleavage site that can be cleaved by furin. Using lentiviral pseudotypes and a cell-culture-adapted SARS-CoV-2 virus with an S1/S2 deletion, we show that the polybasic insertion endows SARS-CoV-2 with a selective advantage in lung cells and primary human airway epithelial cells, but impairs replication in Vero E6, a cell line used for passaging SARS-CoV-2. Using engineered spike variants and live virus competition assays and by measuring growth kinetics, we find that the selective advantage in lung and primary human airway epithelial cells depends on the expression of the cell surface protease TMPRSS2, which enables endosome-independent virus entry by a route that avoids antiviral IFITM proteins. SARS-CoV-2 virus lacking the S1/S2 furin cleavage site was shed to lower titres from infected ferrets and was not transmitted to cohoused sentinel animals, unlike wild-type virus. Analysis of 100,000 SARS-CoV-2 sequences derived from patients and 24 human postmortem tissues showed low frequencies of naturally occurring mutants that harbour deletions at the polybasic site. Taken together, our findings reveal that the furin cleavage site is an important determinant of SARS-CoV-2 transmission.
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