ArticlePLoS biology2023
LRRC15 mediates an accessory interaction with the SARS-CoV-2 spike protein.
Article in PLoS biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- Key regulatory elements of the TGFβ-LRRC15 axis predict disease progression and immunotherapy resistance across cancer types.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Molecular Structure, Expression, and Emerging Role of the 15-Leucine-Rich Repeat Containing Membrane Protein (LRRC15) in Skeletal Biology and Diseases.International journal of molecular sciences · 2026Review
- Dissecting conserved molecular mechanisms of biological toxin activity through CRISPR screening.Biochemical Society transactions · 2026Review
- Structural Basis of MERS-CoV Receptor Interactions and Antibody Neutralisations.Reviews in medical virology · 2026Review
- An adaptable genomic-proteomic approach to characterize cell-surface Vimentin's membrane topology and interactome.Biochemistry and biophysics reports · 2025Article
- Discovery of Proteinaceous Attachment Factors for GII.4 Norovirus from the Diarrheal Sample of a Norovirus-Infected Patient.Food and environmental virology · 2025Article
- Defining diverse spike-receptor interactions involved in SARS-CoV-2 entry: Mechanisms and therapeutic opportunities.Virology · 2025Review
- CRISPR-Cas9 genetic screens reveal regulation of TMPRSS2 by the Elongin BC-VHL complex.Scientific reports · 2025Article
- Analysis of blood proteome in influenza-infected patients reveals new insights into the host response signatures distinguishing mild severe infections.Frontiers in immunology · 2025Article
- Review
- Cell surface protein-protein interaction profiling for biological network analysis and novel target discovery.Life medicine · 2024Review
- Global impact of proteoglycan science on human diseases.iScience · 2023Review
- Receptors and Cofactors That Contribute to SARS-CoV-2 Entry: Can Skin Be an Alternative Route of Entry?International journal of molecular sciences · 2023Review
- Fibroblast-expressed LRRC15 is a receptor for SARS-CoV-2 spike and controls antiviral and antifibrotic transcriptional programs.PLoS biology · 2023Article
- Review
- Multi-omics identify falling LRRC15 as a COVID-19 severity marker and persistent pro-thrombotic signals in convalescence.Nature communications · 2022Article
- LRRC15 inhibits SARS-CoV-2 cellular entry in trans.PLoS biology · 2022Article
- LRRC15 is an inhibitory receptor blocking SARS-CoV-2 spike-mediated entrybioRxiv : the preprint server for biology · 2021Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
The interactions between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and human host factors enable the virus to propagate infections that lead to Coronavirus Disease 2019 (COVID-19). The spike protein is the largest structural component of the virus and mediates interactions essential for infection, including with the primary angiotensin-converting enzyme 2 (ACE2) receptor. We performed two independent cell-based systematic screens to determine whether there are additional proteins by which the spike protein of SARS-CoV-2 can interact with human cells. We discovered that in addition to ACE2, expression of LRRC15 also causes spike protein binding. This interaction is distinct from other known spike attachment mechanisms such as heparan sulfates or lectin receptors. Measurements of orthologous coronavirus spike proteins implied the interaction was functionally restricted to SARS-CoV-2 by accessibility. We localized the interaction to the C-terminus of the S1 domain and showed that LRRC15 shares recognition of the ACE2 receptor binding domain. From analyzing proteomics and single-cell transcriptomics, we identify LRRC15 expression as being common in human lung vasculature cells and fibroblasts. Levels of LRRC15 were greatly elevated by inflammatory signals in the lungs of COVID-19 patients. Although infection assays demonstrated that LRRC15 alone is not sufficient to permit viral entry, we present evidence that it can modulate infection of human cells. This unexpected interaction merits further investigation to determine how SARS-CoV-2 exploits host LRRC15 and whether it could account for any of the distinctive features of COVID-19.
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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.