ArticleProceedings of the National Academy of Sciences of the United States of America2014
Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04420260 (Scheme of Primary Prevention of Infection by COVID-19, in Workers), which is not on this map. Cited by 482 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Scheme of Primary Prevention of Infection by COVID-19, in Workers: Phase II Controlled Clinical Trial, to be Carried Out in Medellín-Antioquia
Who cites it
482 citing papers in PubMed, 1 synthesis or guideline pooled it, 745 citations in OpenAlex.
- The characteristics of gastrointestinal symptoms in patients with severe COVID-19: a systematic review and meta-analysis.Journal of gastroenterology · 2021Pooled it
- Aprotinin treatment against SARS-CoV-2: A randomized phase III study to evaluate the safety and efficacy of a pan-protease inhibitor for moderate COVID-19.European journal of clinical investigation · 2022Trial
- Convergent use of aminopeptidase N receptor by hedgehog merbecoviruses.Nature microbiology · 2026Article
- Disruption of the S1/S2 multibasic cleavage site attenuates infectious bronchitis virus, while S2' partially restores viral virulence and expands tissue tropism.Journal of virology · 2026Article
- Lock out: targeting TMPRSS2 to block influenza and coronaviruses.Journal of virology · 2026Review
- Broad-acting antivirals: the pursuit of pan-viral therapeutics in the era of pandemics.Journal of virology · 2026Review
- Q1020R in the spike proteins of MERS-CoV from Arabian camels confers resistance against soluble human DPP4.Journal of virology · 2026Article
- Pseudovirus-mediated proximity labeling identifies candidate host cell membrane proteins involved in viral attachment.Journal of virology · 2026Article
- Coronavirus M protein disperses the trans-Golgi network and inhibits anterograde protein trafficking in the secretory pathway.PLoS pathogens · 2026Article
- TMPRSS2-mediated coronavirus spike activation and inhibition.Nature structural & molecular biology · 2026Article
- Repertoire-scale antibody structural prediction informs therapeutic design.Science advances · 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
- A natural five-amino-acid insert at the S2' cleavage site of MERS-CoV spike enhances viral membrane fusion.Virologica Sinica · 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
- Characterisation of Naturally Occurring MERS-CoV Spike Mutations and Their Impact on Fusion and Neutralisation.Viruses · 2026Article
- Mutations to the HCoV-229E spike have counterbalancing effects on serum antibody neutralization and receptor binding.bioRxiv : the preprint server for biology · 2026Article
- A stabilized MERS-CoV spike ferritin nanoparticle vaccine elicits robust and protective neutralizing antibody responses.Nature communications · 2026Article
- Structural basis for human DPP4 receptor recognition by MERS-like coronaviruses 2014-422 and GX2012.PLoS pathogens · 2026Article
- Serine protease-driven entry and S2 ' cleavage flexibility of feline coronavirus during feline enterocyte infections.PLoS pathogens · 2026Article
- Bovine coronavirus enters HRT-18 cells via membrane fusion and clathrin-mediated endocytosis in a low pH-, dynamin-, cholesterol-, microtubule-, Rab7-, and Rab11-dependent manner.Journal of virology · 2025Article
422 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
2 authors at 1 institution in 1 country.
Funding
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly identified betacoronavirus causing high morbidity and mortality in humans. The coronavirus spike (S) protein is the main determinant of viral entry, and although it was previously shown that MERS-CoV S can be activated by various proteases, the details of the mechanisms of proteolytic activation of fusion are still incompletely characterized. Here, we have uncovered distinctive characteristics of MERS-CoV S. We identify, by bioinformatics and peptide cleavage assays, two cleavage sites for furin, a ubiquitously expressed protease, which are located at the S1/S2 interface and at the S2' position of the S protein. We show that although the S1/S2 site is proteolytically processed by furin during protein biosynthesis, the S2' site is cleaved upon viral entry. MERS-CoV pseudovirion infection was shown to be enhanced by elevated levels of furin expression, and entry could be decreased by furin siRNA silencing. Enhanced furin activity appeared to partially override the low pH-dependent nature of MERS-CoV entry. Inhibition of furin activity was shown to decrease MERS-CoV S-mediated entry, as well as infection by the virus. Overall, we show that MERS-CoV has evolved an unusual two-step furin activation for fusion, suggestive of a role during the process of emergence into the human population. The ability of MERS-CoV to use furin in this manner, along with other proteases, may explain the polytropic nature of the virus.
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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.