ArticleeLife2021
SARS-CoV-2 S protein:ACE2 interaction reveals novel allosteric targets.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
What it found
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Who cites it
79 citing papers in PubMed.
- A Bifunctional T3SS-Effector Simultaneously Cleaves Host MAP Kinase and Inhibits PPM1A Phosphatase.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dual engagement of Spike and ACE2 by annexin A5 contributes to pleiotropic SARS-CoV-2 inhibition.Scientific reports · 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
- Environmental exposure to air pollution and climate: Intersecting the impact on ear and nose health and chemosensory function (Review).International journal of molecular medicine · 2026Review
- Mutation and ACE2-induced allosteric network rewiring in Delta and Omicron SARS-CoV-2 spike proteins.Biophysical journal · 2026Article
- Natural Fatty Acids as Dual ACE2-Inflammatory Modulators: Integrated Computational Framework for Pandemic Preparedness.International journal of molecular sciences · 2025Article
- Cleaved versus Uncleaved: How furin cleavage reshapes the conformational landscape of SARS-CoV-2 spike.Protein science : a publication of the Protein Society · 2025Article
- Mutation and ACE2-induced Allosteric Network Rewiring in Delta and Omicron SARS-CoV-2 Spike Proteins.bioRxiv : the preprint server for biology · 2025Article
- From Viral Infection to Malignancy: The Dual Threat of EBV and COVID-19 in Cancer Development.Viruses · 2025Review
- Ultrapotent SARS coronavirus-neutralizing single-domain antibodies that clamp the spike at its base.Nature communications · 2025Article
- Capture of fusion-intermediate conformations of SARS-CoV-2 spike requires receptor binding and cleavage at either the S1/S2 or S2' site.PLoS pathogens · 2025Article
- Phosphorylation Modifications and Their Role in Viral Pneumonia: Mechanisms and Therapeutic Implications.Infection and drug resistance · 2025Review
- Development of chimeric MrNV virus-like particles capable of binding to SARS-CoV-2-susceptible cells and reducing infection by pseudovirus variants.Scientific reports · 2024Article
- Conformational dynamics of SARS-CoV-2 Omicron spike trimers during fusion activation at single molecule resolution.Structure (London, England : 1993) · 2024Article
- A protein vaccine of RBD integrated with immune evasion mutation shows broad protection against SARS-CoV-2.Signal transduction and targeted therapy · 2024Article
- Isoform-specific C-terminal phosphorylation drives autoinhibition of Casein kinase 1.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Advances in the Search for SARS-CoV-2 MPathogens (Basel, Switzerland) · 2024Review
- Isoform-specific C-terminal phosphorylation drives autoinhibition of Casein Kinase 1.bioRxiv : the preprint server for biology · 2024Article
- Single-molecule imaging reveals allosteric stimulation of SARS-CoV-2 spike receptor binding domain by host sialic acid.Science advances · 2024Article
- Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
The spike (S) protein is the main handle for SARS-CoV-2 to enter host cells via surface angiotensin-converting enzyme 2 (ACE2) receptors. How ACE2 binding activates proteolysis of S protein is unknown. Here, using amide hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations, we have mapped the S:ACE2 interaction interface and uncovered long-range allosteric propagation of ACE2 binding to sites necessary for host-mediated proteolysis of S protein, critical for viral host entry. Unexpectedly, ACE2 binding enhances dynamics at a distal S1/S2 cleavage site and flanking protease docking site ~27 Å away while dampening dynamics of the stalk hinge (central helix and heptad repeat [HR]) regions ~130 Å away. This highlights that the stalk and proteolysis sites of the S protein are dynamic hotspots in the prefusion state. Our findings provide a dynamics map of the S:ACE2 interface in solution and also offer mechanistic insights into how ACE2 binding is allosterically coupled to distal proteolytic processing sites and viral-host membrane fusion. Thus, protease docking sites flanking the S1/S2 cleavage site represent alternate allosteric hotspot targets for potential therapeutic development.
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Registered trials
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