ArticleProceedings of the National Academy of Sciences of the United States of America2009
Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 639 papers, 3 of them syntheses that pooled it.
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Who cites it
639 citing papers in PubMed, 3 syntheses or guidelines pooled it, 1,166 citations in OpenAlex.
- Organokines in COVID-19: A Systematic Review.Cells · 2023Pooled it
- A systematic review assessing the effectiveness of COVID-19 mRNA vaccines in chronic kidney disease (CKD) individuals.F1000Research · 2022Pooled it
- Promising Antiviral Activities of Natural Flavonoids against SARS-CoV-2 Targets: Systematic Review.International journal of molecular sciences · 2021Pooled it
- Aminopeptidase N is a receptor for hedgehog merbecoviruses.Nature microbiology · 2026Article
- Structural and functional characterization of a conserved cryptic epitope on SARS-CoV-2 spike S2 subunit.PLoS pathogens · 2026Article
- Concanavalin A targets phylogenetically conserved N-linked glycans on coronavirus spike proteins for broad-spectrum antiviral activity.Journal of virology · 2026Article
- TMPRSS2-mediated coronavirus spike activation and inhibition.Nature structural & molecular biology · 2026Article
- Coronavirus M protein disperses the trans-Golgi network and inhibits anterograde protein trafficking in the secretory pathway.PLoS pathogens · 2026Article
- An Ad5-Based COVID-19 Vaccine Encoding SARS-CoV-2 Spike Glycoprotein Induces Measurable Antibody and Cytokine Responses in Mice.Biotechnology journal · 2026Article
- Structural Basis of MERS-CoV Receptor Interactions and Antibody Neutralisations.Reviews in medical virology · 2026Review
- Mutations to the HCoV-229E spike have counterbalancing effects on serum antibody neutralization and receptor binding.bioRxiv : the preprint server for biology · 2026Article
- Cavity-Filling Mutations as a Strategy to Stabilize Prefusion Viral Fusion Proteins for Vaccine Design.Computational and structural biotechnology journal · 2026Review
- Effect of the S2' site cleavage on SARS-CoV-2 spike.Nature communications · 2025Article
- Bat sarbecovirus WIV1-CoV bears an adaptive mutation that alters spike dynamics and enhances ACE2 binding.PLoS pathogens · 2025Article
- An orally available MNature communications · 2025Article
- Mycophenolic acid treatment drives the emergence of novel SARS-CoV-2 variants.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Unveiling the structural spectrum of SARS-CoV-2 fusion by in situ cryo-ET.Nature communications · 2025Article
- Host susceptibilities and entry processes of SARS-CoV-2 Omicron variants using pseudotyped viruses carrying spike protein.BMC veterinary research · 2025Article
- Development of Anti-idiotypic Monoclonal Antibody Mimicking SARS-CoV-2 Receptor Binding Domain.Molecular biotechnology · 2025Article
- Role of furin in the severity of COVID-19 infection via effects on miR-20b and miR-106a.Molecular biology reports · 2025Article
579 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The coronavirus spike protein (S) plays a key role in the early steps of viral infection, with the S1 domain responsible for receptor binding and the S2 domain mediating membrane fusion. In some cases, the S protein is proteolytically cleaved at the S1-S2 boundary. In the case of the severe acute respiratory syndrome coronavirus (SARS-CoV), it has been shown that virus entry requires the endosomal protease cathepsin L; however, it was also found that infection of SARS-CoV could be strongly induced by trypsin treatment. Overall, in terms of how cleavage might activate membrane fusion, proteolytic processing of the SARS-CoV S protein remains unclear. Here, we identify a proteolytic cleavage site within the SARS-CoV S2 domain (S2', R797). Mutation of R797 specifically inhibited trypsin-dependent fusion in both cell-cell fusion and pseudovirion entry assays. We also introduced a furin cleavage site at both the S2' cleavage site within S2 793-KPTKR-797 (S2'), as well as at the junction of S1 and S2. Introduction of a furin cleavage site at the S2' position allowed trypsin-independent cell-cell fusion, which was strongly increased by the presence of a second furin cleavage site at the S1-S2 position. Taken together, these data suggest a novel priming mechanism for a viral fusion protein, with a critical proteolytic cleavage event on the SARS-CoV S protein at position 797 (S2'), acting in concert with the S1-S2 cleavage site to mediate membrane fusion and virus infectivity.
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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.