ArticleProceedings of the National Academy of Sciences of the United States of America2022
SARS-CoV-2 spike engagement of ACE2 primes S2' site cleavage and fusion initiation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 128 citations in OpenAlex.
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- Intelligent Programmable Membrane Nanosponge for Early Virus Blocking.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Antiviral activity of Saponin C from Liriope muscari against influenza A virus and SARS-CoV-2.Virologica Sinica · 2026Article
- Concanavalin A targets phylogenetically conserved N-linked glycans on coronavirus spike proteins for broad-spectrum antiviral activity.Journal of virology · 2026Article
- Article
- TMPRSS2-mediated coronavirus spike activation and inhibition.Nature structural & molecular biology · 2026Article
- TNF inhibits SARS-CoV-2 induced cell-cell fusion through activating the SDC4-RhoA signaling to promote actin bundles formation.Cell insight · 2026Article
- Mutations to the HCoV-229E spike have counterbalancing effects on serum antibody neutralization and receptor binding.bioRxiv : the preprint server for biology · 2026Article
- Mutation and ACE2-induced allosteric network rewiring in Delta and Omicron SARS-CoV-2 spike proteins.Biophysical journal · 2026Article
- The Enigmatic Conserved Q134-F135-N137 Triad in SARS-CoV-2 Spike Protein: A Conformational Transducer?Biomolecules · 2026Review
- Serine protease-driven entry and S2 ' cleavage flexibility of feline coronavirus during feline enterocyte infections.PLoS pathogens · 2026Article
- Interferon-stimulated gene GALNT2 restricts respiratory virus infections.Nature microbiology · 2026Article
- Conformational bias in SARS-CoV-2 Spike CD4+ T-cell epitope dominance.Frontiers in immunology · 2026Article
- LL-37 Inhibits TMPRSS2-Mediated S2' Site Cleavage and SARS-CoV-2 Infection but Not Omicron Variants.Cell proliferation · 2025Article
- Receptor affinity-selective differential dynamics of membrane fusion initiation govern deltacoronavirus cross-species transmission.Science China. Life sciences · 2025Article
- Effect of COVID-19 infection on thyroid function status and clinical indexes among hypothyroid outpatients.Virulence · 2025Article
- Mutation and ACE2-induced Allosteric Network Rewiring in Delta and Omicron SARS-CoV-2 Spike Proteins.bioRxiv : the preprint server for biology · 2025Article
- ACE2-Decoy-Conjugated PLGA-PEG Nanoparticles Loaded with Nafamostat for Potent Antiviral Activity.Viruses · 2025Article
- TMEM106B Supports Viral Entry and Syncytia Formation Mediated by the Spike Proteins From Omicron BA.2.86 and JN.1.Journal of medical virology · 2025Article
- Receptor Binding for the Entry Mechanisms of SARS-CoV-2: Insights from the Original Strain and Emerging Variants.Viruses · 2025Review
27 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in tremendous loss worldwide. Although viral spike (S) protein binding of angiotensin-converting enzyme 2 (ACE2) has been established, the functional consequences of the initial receptor binding and the stepwise fusion process are not clear. By utilizing a cell-cell fusion system, in complement with a pseudoviral infection model, we found that the spike engagement of ACE2 primed the generation of S2' fragments in target cells, a key proteolytic event coupled with spike-mediated membrane fusion. Mutagenesis of an S2' cleavage site at the arginine (R) 815, but not an S2 cleavage site at arginine 685, was sufficient to prevent subsequent syncytia formation and infection in a variety of cell lines and primary cells isolated from human ACE2 knock-in mice. The requirement for S2' cleavage at the R815 site was also broadly shared by other SARS-CoV-2 spike variants, such as the Alpha, Beta, and Delta variants of concern. Thus, our study highlights an essential role for host receptor engagement and the key residue of spike for proteolytic activation, and uncovers a targetable mechanism for host cell infection by SARS-CoV-2.
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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.