ArticleThe EMBO journal2021
TMPRSS2 expression dictates the entry route used by SARS-CoV-2 to infect host cells.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 245 papers, 2 of them syntheses that pooled it.
What it found
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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
245 citing papers in PubMed, 2 syntheses or guidelines pooled it, 361 citations in OpenAlex.
- Safety and Efficacy of Camostat Mesylate for Covid-19: a systematic review and Meta-analysis of Randomized controlled trials.BMC infectious diseases · 2024Pooled it
- Bidirectional genome-wide CRISPR screens reveal host factors regulating SARS-CoV-2, MERS-CoV and seasonal HCoVs.Nature genetics · 2022Pooled it
- One Week of Oral Camostat Versus Placebo in Nonhospitalized Adults With Mild-to-Moderate Coronavirus Disease 2019: A Randomized Controlled Phase 2 Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Trial
- Disulfide bonds stabilize the SARS-CoV-2 RBD and preserve binding to ACE2 following thermal denaturation.Bioscience reports · 2026Article
- ACE2-PNA conjugates exploit viral endocytosis for targeted intracellular delivery and exhibit dual antiviral efficacy against SARS-CoV-2.Molecular biomedicine · 2026Article
- Targeted IL-27-based gene therapy in preventing SARS-CoV-2 entry.Molecular biology reports · 2026Article
- Repurposing screens reveal a role for PKCη and NF1 in SARS-CoV-2 infection.PLoS pathogens · 2026Article
- DNA oligonucleotides block viral entry of SARS-CoV-2 Omicron variants.PLoS pathogens · 2026Article
- Lock out: targeting TMPRSS2 to block influenza and coronaviruses.Journal of virology · 2026Review
- In Silico Modeling of Structural Compatibility and Alignment Between Viral Class I Fusion Cores and Human TLR4/MD-2.International journal of molecular sciences · 2026Article
- Pilot survey among patients taking bromhexine prophylactically against influenza.Journal of family medicine and primary care · 2026Article
- TMPRSS2-induced Golgi disruption restricts the incorporation of virus envelope glycoproteins into virions.EMBO reports · 2026Article
- Article
- How endosomal PIKfyve inhibition prevents viral membrane fusion and entry.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Inhibition of host N-myristoylation compromises the infectivity of SARS-CoV-2 due to Golgi-bypassing egress.Nature communications · 2026Article
- CGM23 corresponds to a pan-coronavirus lipopeptide inhibitor potently inhibiting virion fusion.iScience · 2026Article
- Uptake of Nanoparticles as a Model System for Viruses under the Presence of Chloroquine.ACS nanoscience Au · 2026Article
- Species- and variant-specific ACE2 compatibility shapes SARS-CoV-2 spillover potential in North American cervids.Nature communications · 2026Article
- Clade C MERS-CoV camel strains vary in protease utilization during viral entry.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Entry, replication and innate immunity evasion of BANAL-236, a SARS-CoV-2-related bat virus, in Rhinolophus and human cells.PLoS pathogens · 2026Article
185 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
6 authors at 3 institutions in 2 countries.
Funding
Abstract
SARS-CoV-2 is a newly emerged coronavirus that caused the global COVID-19 outbreak in early 2020. COVID-19 is primarily associated with lung injury, but many other clinical symptoms such as loss of smell and taste demonstrated broad tissue tropism of the virus. Early SARS-CoV-2-host cell interactions and entry mechanisms remain poorly understood. Investigating SARS-CoV-2 infection in tissue culture, we found that the protease TMPRSS2 determines the entry pathway used by the virus. In the presence of TMPRSS2, the proteolytic process of SARS-CoV-2 was completed at the plasma membrane, and the virus rapidly entered the cells within 10 min in a pH-independent manner. When target cells lacked TMPRSS2 expression, the virus was endocytosed and sorted into endolysosomes, from which SARS-CoV-2 entered the cytosol via acid-activated cathepsin L protease 40-60 min post-infection. Overexpression of TMPRSS2 in non-TMPRSS2 expressing cells abolished the dependence of infection on the cathepsin L pathway and restored sensitivity to the TMPRSS2 inhibitors. Together, our results indicate that SARS-CoV-2 infects cells through distinct, mutually exclusive entry routes and highlight the importance of TMPRSS2 for SARS-CoV-2 sorting into either pathway.
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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.