ArticleeLife2022
Coagulation factors directly cleave SARS-CoV-2 spike and enhance viral entry.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis 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
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 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
- Blood Coagulation in COVID-19: Systems-Biology Evidence, Clinical Implications, and Therapeutic Opportunities in an Evolving Pandemic.ACS omega · 2026Article
- Species- and variant-specific ACE2 compatibility shapes SARS-CoV-2 spillover potential in North American cervids.Nature communications · 2026Article
- Development of ketobenzothiazole-based peptidomimetic TMPRSS13 inhibitors with low nanomolar potency.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Article
- The Role of Long-Range Non-Specific Electrostatic Interactions in Inhibiting the Pre-Fusion Proteolytic Processing of the SARS-CoV-2 S Glycoprotein by Heparin.Biomolecules · 2025Article
- Betrixaban is a broad anti-virus inhibitor by activating innate immunity.Frontiers in cellular and infection microbiology · 2025Article
- Host proteases: key regulators in viral infection and therapeutic targeting.Frontiers in immunology · 2025Review
- Host Cell Proteases Involved in Human Respiratory Viral Infections and Their Inhibitors: A Review.Viruses · 2024Review
- Genome-wide bioinformatics analysis of human protease capacity for proteolytic cleavage of the SARS-CoV-2 spike glycoprotein.Microbiology spectrum · 2024Article
- Unravelling the impact of SARS-CoV-2 on hemostatic and complement systems: a systems immunology perspective.Frontiers in immunology · 2024Article
- Risk Factors for Long COVID in Older Adults.Biomedicines · 2023Review
- RAndomized Clinical Trial Of NAfamostat Mesylate, A Potent Transmembrane Protease Serine 2 (TMPRSS2) Inhibitor, in Patients with COVID-19 Pneumonia.Journal of clinical medicine · 2023Article
- Article
- Dimethyl fumarate and 4-octyl itaconate are anticoagulants that suppress Tissue Factor in macrophages via inhibition of Type I Interferon.Nature communications · 2023Article
- Article
- Aged brain and neuroimmune responses to COVID-19: post-acute sequelae and modulatory effects of behavioral and nutritional interventions.Immunity & ageing : I & A · 2023Review
- Factor Xa cleaves SARS-CoV-2 spike protein to block viral entry and infection.Nature communications · 2023Article
- COVID-19 and Diarylamidines: The Parasitic Connection.International journal of molecular sciences · 2023Review
- Review
Corrections and comments
- Update of
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Coagulopathy is a significant aspect of morbidity in COVID-19 patients. The clotting cascade is propagated by a series of proteases, including factor Xa and thrombin. While certain host proteases, including TMPRSS2 and furin, are known to be important for cleavage activation of SARS-CoV-2 spike to promote viral entry in the respiratory tract, other proteases may also contribute. Using biochemical and cell-based assays, we demonstrate that factor Xa and thrombin can also directly cleave SARS-CoV-2 spike, enhancing infection at the stage of viral entry. Coagulation factors increased SARS-CoV-2 infection in human lung organoids. A drug-repurposing screen identified a subset of protease inhibitors that promiscuously inhibited spike cleavage by both transmembrane serine proteases and coagulation factors. The mechanism of the protease inhibitors nafamostat and camostat may extend beyond inhibition of TMPRSS2 to coagulation-induced spike cleavage. Anticoagulation is critical in the management of COVID-19, and early intervention could provide collateral benefit by suppressing SARS-CoV-2 viral entry. We propose a model of positive feedback whereby infection-induced hypercoagulation exacerbates SARS-CoV-2 infectivity.
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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.