ArticleThe Journal of biological chemistry2006
SARS coronavirus, but not human coronavirus NL63, utilizes cathepsin L to infect ACE2-expressing cells.
Article in The Journal of biological chemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 259 papers, 4 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
259 citing papers in PubMed, 4 syntheses or guidelines pooled it, 386 citations in OpenAlex.
- Single-cell analysis of adult human heart across healthy and cardiovascular disease patients reveals the cellular landscape underlying SARS-CoV-2 invasion of myocardial tissue through ACE2.Journal of translational medicine · 2023Pooled it
- Bidirectional genome-wide CRISPR screens reveal host factors regulating SARS-CoV-2, MERS-CoV and seasonal HCoVs.Nature genetics · 2022Pooled it
- COVID-19 outbreak: history, mechanism, transmission, structural studies and therapeutics.Infection · 2021Pooled it
- Pooled it
- Nanoscopy reveals heparan sulfate clusters as docking sites for SARS-CoV-2 attachment and entry.eLife · 2026Article
- Exploring coronavirus cell entry with functional viromics.Journal of virology · 2026Review
- Endolysosomal trafficking regulator SH-BC-893 inhibits coronavirus entry in vitro and in vivo.Scientific reports · 2026Article
- B Cell Receptor's function in virus entry: Anti-SARS-CoV-2 B cell receptors can mediate viral entry in an ACE2-independent mechanism.PLoS pathogens · 2026Article
- Identification of Cathepsin L as the Molecular Target of Hydroxychloroquine With Chemical Proteomics.Molecular & cellular proteomics : MCP · 2025Article
- Production of human cathepsins using Expi293™ mammalian cell expression system for off-target activity of cysteine protease inhibitor screening.Protein science : a publication of the Protein Society · 2025Article
- Bat sarbecovirus WIV1-CoV bears an adaptive mutation that alters spike dynamics and enhances ACE2 binding.PLoS pathogens · 2025Article
- Nanoscopy Reveals Heparan Sulfate Clusters as Docking Sites for SARS-CoV-2 Attachment and Entry.bioRxiv : the preprint server for biology · 2025Article
- Unveiling the structural spectrum of SARS-CoV-2 fusion by in situ cryo-ET.Nature communications · 2025Article
- Unraveling the COVID-19 Severity Hubs and Interplays in Inflammatory-Related RNA-Protein Networks.International journal of molecular sciences · 2025Article
- Cathepsins in cellular entry of human pathogenic viruses.Journal of virology · 2025Review
- Characterization of spike S1/S2 processing and entry pathways of lentiviral pseudoviruses bearing seasonal human coronaviruses NL63, 229E, and HKU1 spikes.Microbiology spectrum · 2025Article
- Cellular sialoglycans are differentially required for endosomal and cell-surface entry of SARS-CoV-2 in lung cell lines.PLoS pathogens · 2024Article
- Comprehensive Risk Assessment of Infection Induced by SARS-CoV-2.Molecular neurobiology · 2024Review
- Cholesterol and Cholesterol-Lowering Medications in COVID-19-An Unresolved Matter.International journal of molecular sciences · 2024Review
- Simultaneous screening for selective SARS-CoV-2, Lassa, and Machupo virus entry inhibitors.SLAS discovery : advancing life sciences R & D · 2024Article
199 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Viruses require specific cellular receptors to infect their target cells. Angiotensin-converting enzyme 2 (ACE2) is a cellular receptor for two divergent coronaviruses, SARS coronavirus (SARS-CoV) and human coronavirus NL63 (HCoV-NL63). In addition to hostcell receptors, lysosomal cysteine proteases are required for productive infection by some viruses. Here we show that SARS-CoV, but not HCoV-NL63, utilizes the enzymatic activity of the cysteine protease cathepsin L to infect ACE2-expressing cells. Inhibitors of cathepsin L blocked infection by SARS-CoV and by a retrovirus pseudotyped with the SARS-CoV spike (S) protein but not infection by HCoV-NL63 or a retrovirus pseudotyped with the HCoV-NL63 S protein. Expression of exogenous cathepsin L substantially enhanced infection mediated by the SARS-CoV S protein and by filovirus GP proteins but not by the HCoV-NL63 S protein or the vesicular stomatitis virus G protein. Finally, an inhibitor of endosomal acidification had substantially less effect on infection mediated by the HCoV-NL63 S protein than on that mediated by the SARS-CoV S protein. Our data indicate that two coronaviruses that utilize a common receptor nonetheless enter cells through distinct mechanisms.
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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.