ArticlePathogens & immunity2021
Alpha 1 Antitrypsin is an Inhibitor of the SARS-CoV-2-Priming Protease TMPRSS2.
Article in Pathogens & immunity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed.
- A randomized, double-blind, placebo-controlled trial of intravenous alpha-1 antitrypsin for ARDS secondary to COVID-19.Med (New York, N.Y.) · 2022Trial
- COVID-19 outcomes in individuals with severe alpha-1 antitrypsin deficiency in Sweden.Scientific reports · 2026Article
- Role of the alpha-1 antitrypsin in the progression and severity of COVID-19 infection among Saudi patients.BMC infectious diseases · 2025Article
- Simulations and active learning enable efficient identification of an experimentally-validated broad coronavirus inhibitor.Nature communications · 2025Article
- Coronavirus disease 2019-associated liver injury in pregnancy: A case report.The Journal of international medical research · 2025Article
- Host proteases: key regulators in viral infection and therapeutic targeting.Frontiers in immunology · 2025Review
- 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
- Analysis of alpha-1-antitrypsin (AAT)-regulated, glucocorticoid receptor-dependent genes in macrophages reveals a novel host defense function of AAT.Physiological reports · 2024Article
- Aprotinin (II): Inhalational Administration for the Treatment of COVID-19 and Other Viral Conditions.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
- Neutrophil proteases are protective against SARS-CoV-2 by degrading the spike protein and dampening virus-mediated inflammation.JCI insight · 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
- COVID-19 in Individuals with Severe Alpha 1-Antitrypsin Deficiency.International journal of chronic obstructive pulmonary disease · 2024Article
- Impact of the COVID-19 pandemic on well-being and quality of life of patients with alpha-1-antitrypsin deficiency.Respiratory research · 2023Article
- Plant Serpins: Potential Inhibitors of Serine and Cysteine Proteases with Multiple Functions.Plants (Basel, Switzerland) · 2023Review
- Meditation-induced bloodborne factors as an adjuvant treatment to COVID-19 disease.Brain, behavior, & immunity - health · 2023Article
- 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
- Strategies for the Management of Spike Protein-Related Pathology.Microorganisms · 2023Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHost proteases have been suggested to be crucial for dissemination of MERS, SARS-CoV, and SARS-CoV-2 coronaviruses, but the relative contribution of membrane versus intracellular proteases remains controversial. Transmembrane serine protease 2 (TMPRSS2) is regarded as one of the main proteases implicated in the coronavirus S protein priming, an important step for binding of the S protein to the angiotensin-converting enzyme 2 (ACE2) receptor before cell entry.
methodsWe developed a cell-based assay to identify TMPRSS2 inhibitors. Inhibitory activity was established in SARS-CoV-2 viral load systems.
resultsWe identified the human extracellular serine protease inhibitor (serpin) alpha 1 anti-trypsin (A1AT) as a novel TMPRSS2 inhibitor. Structural modeling revealed that A1AT docked to an extracellular domain of TMPRSS2 in a conformation that is suitable for catalysis, resembling similar serine protease inhibitor complexes. Inhibitory activity of A1AT was established in a SARS-CoV-2 viral load system. Notably, plasma A1AT levels were associated with COVID-19 disease severity.
conclusionsOur data support the key role of extracellular serine proteases in SARS CoV-2 infections and indicate that treatment with serpins, particularly the FDA-approved drug A1AT, may be effective in limiting SARS-CoV-2 dissemination by affecting the surface of the host cells.
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