ReviewMicrobiology and immunology2022
Proteolytic activation of SARS-CoV-2 spike protein.
Review in Microbiology and immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
118 citing papers in PubMed, 2 syntheses or guidelines pooled it, 191 citations in OpenAlex.
- Polymorphism of tmprss2 (rs12329760) but not ace2 (rs4240157), tmprss11a (rs353163) and cd147 (rs8259) is associated with the severity of COVID-19 in the Ukrainian population.Acta bio-medica : Atenei Parmensis · 2023Pooled it
- Pooled it
- Molecular Insights into High-Pathogenicity RNA Viruses.Viruses · 2026Review
- Super-resolution atlas of SARS-CoV-2 infection reveals protease-dependent organelle maturation, dsRNA landscapes, and intracellular structural proteins.Nature communications · 2026Article
- TMPRSS2-induced Golgi disruption restricts the incorporation of virus envelope glycoproteins into virions.EMBO reports · 2026Article
- SARS-CoV-2 Omicron variant spike protein maintains the ability to bind and activate human platelets: Comparison with the wild-type.Scientific reports · 2026Article
- HLA-C-derived peptide MH-1 as an early-stage intervention against SARS-CoV-2 infection.Molecular medicine (Cambridge, Mass.) · 2026Article
- A Double-Edged Sword: Extracellular Serine Proteases as Facilitators of Infection and Mediators of Immunity.Molecules (Basel, Switzerland) · 2026Review
- The Enigmatic Conserved Q134-F135-N137 Triad in SARS-CoV-2 Spike Protein: A Conformational Transducer?Biomolecules · 2026Review
- Comparative progress on the mechanisms of airway mucosal injury induced by different pathogens: SARS-CoV-2, influenza A virus, and Mycoplasma pneumoniae.Frontiers in cellular and infection microbiology · 2026Review
- Cleaved versus Uncleaved: How furin cleavage reshapes the conformational landscape of SARS-CoV-2 spike.Protein science : a publication of the Protein Society · 2025Article
- Exploiting viral infection/vaccination to focus high-affinity T cell populations into tumors using oncolytic viro-immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Anti-Oxidant, Anti-Inflammatory and Antiviral Properties of Luteolin Against SARS-CoV-2: Based on Network Pharmacology.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Molecular and pathological confirmation of natural feline coronavirus infection in a captive persian leopard (Open veterinary journal · 2025Article
- Review
- The Molecular Mechanisms of Cognitive Dysfunction in Long COVID: A Narrative Review.International journal of molecular sciences · 2025Review
- Role of N-linked glycosylation sites in human ACE2 in SARS-CoV-2 and hCoV-NL63 infection.Journal of virology · 2025Article
- Receptor Binding for the Entry Mechanisms of SARS-CoV-2: Insights from the Original Strain and Emerging Variants.Viruses · 2025Review
- Article
- CRISPR-Cas9 genetic screens reveal regulation of TMPRSS2 by the Elongin BC-VHL complex.Scientific reports · 2025Article
58 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
1 author at 1 institution in 1 country.
Funding
Abstract
Spike (S) protein cleavage is a crucial step in coronavirus infection. In this review, this process is discussed, with particular focus on the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Compared with influenza virus and paramyxovirus membrane fusion proteins, the cleavage activation mechanism of coronavirus S protein is much more complex. The S protein has two cleavage sites (S1/S2 and S2'), and the cleavage motif for furin protease at the S1/S2 site that results from a unique four-amino acid insertion is one of the distinguishing features of SARS-CoV-2. The viral particle incorporates the S protein, which has already undergone S1/S2 cleavage by furin, and then undergoes further cleavage at the S2' site, mediated by the type II transmembrane serine protease transmembrane protease serine 2 (TMPRSS2), after binding to the receptor angiotensin-converting enzyme 2 (ACE2) to facilitate membrane fusion at the plasma membrane. In addition, SARS-CoV-2 can enter the cell by endocytosis and be proteolytically activated by cathepsin L, although this is not a major mode of SARS-CoV-2 infection. SARS-CoV-2 variants with enhanced infectivity have been emerging throughout the ongoing pandemic, and there is a close relationship between enhanced infectivity and changes in S protein cleavability. All four variants of concern carry the D614G mutation, which indirectly enhances S1/S2 cleavability by furin. The P681R mutation of the delta variant directly increases S1/S2 cleavability, enhancing membrane fusion and SARS-CoV-2 virulence. Changes in S protein cleavability can significantly impact viral infectivity, tissue tropism, and virulence. Understanding these mechanisms is critical to counteracting the coronavirus pandemic.
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What OpenQuestion holds
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.