ArticlemBio2022
Serine Protease Inhibitors Restrict Host Susceptibility to SARS-CoV-2 Infections.
Article in mBio, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- Lock out: targeting TMPRSS2 to block influenza and coronaviruses.Journal of virology · 2026Review
- Cartilage intermediate layer protein inhibits ligamentum flavum hypertrophy mediated by TGF-β1/SMAD3/SERPINE2 signaling pathway.Cellular and molecular life sciences : CMLS · 2026Article
- Transcriptomic profiling reveals immune signatures associated with potential COVID-19 susceptibility and a predictive framework in a Chinese cohort.Frontiers in immunology · 2026Article
- SARS-CoV-2 infection in hiPSC-derived neurons is cathepsin-dependent and causes differential accumulation of HIF1ɑ and phosphorylated tau.Molecular therapy. Nucleic acids · 2025Article
- Host cell and viral protease targets of human SERPINs identified by in silico docking.The EMBO journal · 2025Article
- SerpinB3/Protease Activated Receptor-2 Axis Is Essential for SARS CoV-2 Infection.ACS infectious diseases · 2025Article
- METTL3 stabilizes SERPINE2 via the m6A modification to drive the malignant progression of gastric signet ring cell carcinoma.Translational cancer research · 2025Article
- Alternative Matrices for Protein Biomarker Analysis by qPCR Using Proximity Extension Assay (PEA).Methods in molecular biology (Clifton, N.J.) · 2025Article
- Heightened Innate Immune and Inflammatory Gene Expression in the Skin of Severe COVID-19 Cases.Journal of inflammation research · 2025Article
- Article
- Aprotinin (I): Understanding the Role of Host Proteases in COVID-19 and the Importance of Pharmacologically Regulating Their Function.International journal of molecular sciences · 2024Review
- A reduced proteomic signature in critically ill Covid-19 patients determined with plasma antibody micro-array and machine learning.Clinical proteomics · 2024Article
- Review
- The Inhibition of Serine Proteases by Serpins Is Augmented by Negatively Charged Heparin: A Concise Review of Some Clinically Relevant Interactions.International journal of molecular sciences · 2024Review
- Salivary IgA and vimentin differentiate in vitro SARS-CoV-2 infection: A study of 290 convalescent COVID-19 patients.Mucosal immunology · 2024Article
- Suppressed transcript diversity and immune response in COVID-19 ICU patients: a longitudinal study.Life science alliance · 2024Article
- The fatal contribution of serine protease-related genetic variants to COVID-19 outcomes.Frontiers in immunology · 2024Article
- Inhibition of Infectious HIV-1 Production by Rerouting the Cellular Furin Inhibitor Serpin B8.Journal of virology · 2023Article
- Alpha-1-antitrypsin antagonizes COVID-19: a review of the epidemiology, molecular mechanisms, and clinical evidence.Biochemical Society transactions · 2023Review
- TMPRSS2 Inhibitor Discovery Facilitated through anACS medicinal chemistry letters · 2023Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The coronavirus disease 2019, COVID-19, is a complex disease with a wide range of symptoms from asymptomatic infections to severe acute respiratory syndrome with lethal outcome. Individual factors such as age, sex, and comorbidities increase the risk for severe infections, but other aspects, such as genetic variations, are also likely to affect the susceptibility to SARS-CoV-2 infection and disease severity. Here, we used a human 3D lung cell model based on primary cells derived from multiple donors to identity host factors that regulate SARS-CoV-2 infection. With a transcriptomics-based approach, we found that less susceptible donors show a higher expression level of serine protease inhibitors SERPINA1, SERPINE1, and SERPINE2, identifying variation in cellular serpin levels as restricting host factors for SARS-CoV-2 infection. We pinpoint their antiviral mechanism of action to inhibition of the cellular serine protease, TMPRSS2, thereby preventing cleavage of the viral spike protein and TMPRSS2-mediated entry into the target cells. By means of single-cell RNA sequencing, we further locate the expression of the individual serpins to basal, ciliated, club, and goblet cells. Our results add to the importance of genetic variations as determinants for SARS-CoV-2 susceptibility and suggest that genetic deficiencies of cellular serpins might represent risk factors for severe COVID-19. Our study further highlights TMPRSS2 as a promising target for antiviral intervention and opens the door for the usage of locally administered serpins as a treatment against COVID-19.
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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.