ArticleCell2024
Human coronavirus HKU1 recognition of the TMPRSS2 host receptor.
Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
- TMPRSS2 inhibitors with broad-spectrum efficacy against SARS-CoV-2 (JN.1) and influenza A (H1N1) viruses protect mice from influenza A infection.Emerging microbes & infections · 2026Article
- Discovery of Highly Selective Noncovalent Macrocyclic Peptide Inhibitors Suppressing Both TMPRSS2 Protease Activity and Viral Receptor Function.Journal of medicinal chemistry · 2026Article
- Temperature-dependent replication and sensitivity to innate immunity of human coronavirus HKU1.Nature communications · 2026Article
- Lock out: targeting TMPRSS2 to block influenza and coronaviruses.Journal of virology · 2026Review
- Isolation and characterization of LH5, a novel rodent Embecovirus from Rattus tanezumi with respiratory tropism in a mouse model.BMC biology · 2026Article
- OC43 clinical isolate spike proteins have distinct carbohydrate-binding properties.Nature communications · 2026Article
- Establishment of a human coronavirus HKU1 infection evaluation system using apical-out airway organoids.The Journal of general virology · 2026Article
- TMPRSS2-mediated coronavirus spike activation and inhibition.Nature structural & molecular biology · 2026Article
- Cetacean coronavirus spikes highlight S glycoprotein structural plasticity.PLoS pathogens · 2026Article
- Antagonistic Ubiquitin Switching by USP7 and RNF40 Orchestrates KDM6A Homeostasis to License Coronavirus Susceptibility.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- AI-guided prefusion stabilization of the human coronavirus OC43 spike protein enables universal embecovirus antigen design.PLoS pathogens · 2026Article
- 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
- Rational Design of Multiclade Coronavirus Spike Immunodominant Domain Nanoparticles to Elicit Broad Antibody Responses.Research square · 2025Article
- An integrated workflow for structural virology with a 100 keV electron microscope.bioRxiv : the preprint server for biology · 2025Article
- Effect of the S2' site cleavage on SARS-CoV-2 spike.Nature communications · 2025Article
- Current Status and Challenges of Vaccine Development for Seasonal Human Coronaviruses.Vaccines · 2025Review
- From zoonotic spillover to endemicity: the broad determinants of human coronavirus tropism.mBio · 2025Review
- Human coronavirus HKU1 neutralization by glycan receptor mimicry.bioRxiv : the preprint server for biology · 2025Article
- Dipeptidase 1 is a functional receptor for a porcine coronavirus.Nature microbiology · 2025Article
- Human Coronavirus HKU1 Neutralizing Monoclonal Antibodies Target Diverse Epitopes Within and Around the TMPRSS2 Receptor Binding Site.bioRxiv : the preprint server for biology · 2025Article
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Authors and funding
12 authors.
Funding
Abstract
The human coronavirus HKU1 spike (S) glycoprotein engages host cell surface sialoglycans and transmembrane protease serine 2 (TMPRSS2) to initiate infection. The molecular basis of HKU1 binding to TMPRSS2 and determinants of host receptor tropism remain elusive. We designed an active human TMPRSS2 construct enabling high-yield recombinant production in human cells of this key therapeutic target. We determined a cryo-electron microscopy structure of the HKU1 RBD bound to human TMPRSS2, providing a blueprint of the interactions supporting viral entry and explaining the specificity for TMPRSS2 among orthologous proteases. We identified TMPRSS2 orthologs from five mammalian orders promoting HKU1 S-mediated entry into cells along with key residues governing host receptor usage. Our data show that the TMPRSS2 binding motif is a site of vulnerability to neutralizing antibodies and suggest that HKU1 uses S conformational masking and glycan shielding to balance immune evasion and receptor engagement.
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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.