Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (688 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Plasma glycoprotein member of the serpin superfamily which inhibits trypsin; neutrophil elastase; and other proteolytic enzymes.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: alpha 1 Antitrypsin; alpha 1-Protease Inhibitor; alpha 1 Protease Inhibitor; Inhibitor, alpha 1-Protease; Trypsin Inhibitor, alpha 1-Antitrypsin; Trypsin Inhibitor, alpha 1 Antitrypsin; alpha 1 Antiprotease; Antiprotease, alpha 1.
Where it fits in the MeSH classification
- Broader topics
- Glycoproteins; Serpins; Acute-Phase Proteins; Alpha-Globulins
- See also
- alpha 1-Antitrypsin Deficiency
Related concepts
- Trypsin
- Neutrophil Elastase
- Proteolytic Enzymes
Research landscape
PubMed indexes 9,367 records tagged with the MeSH heading “alpha 1-Antitrypsin” (counts retrieved 2026-10-31). 719 of them (7.7%) were published from 2020 onward, and the busiest period so far is through 1999 with 5,719 records.
Reviews account for 785 records (8.4%) and meta-analyses for 22. Randomized controlled trials number 97 (1.0%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 5,719 |
| 2000-2009 | 1,508 |
| 2010-2019 | 1,421 |
| 2020 onward | 719 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 785 | 8.4% |
| Meta-analyses | 22 | 0.2% |
| Randomized controlled trials | 97 | 1.0% |
Method: PubMed query "alpha 1-Antitrypsin"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Alpha-1 antitrypsin inhibits TMPRSS2 protease activity and SARS-CoV-2 infection | 2021 | Research article Design not recorded in structured metadata | 125 | cc by PMID 33741941 · DOI · PMC7979852 |
| Alpha-1 antitrypsin deficiency: outstanding questions and future directions | 2018 | Review article Design not recorded in structured metadata | 84 | cc by PMID 29996870 · DOI · PMC6042212 |
| Comprehensive analysis of prime editing outcomes in human embryonic stem cells | 2022 | Research article Design not recorded in structured metadata | 77 | cc by PMID 35018468 · DOI · PMC8789035 |
| Circulating alpha-1 antitrypsin and its c-terminal peptides differentiate bacterial from viral community-acquired pneumonia | 2026 | Research article Design not recorded in structured metadata | 0 | cc by PMID 42477702 · DOI · PMC13390320 |
Alpha-1 antitrypsin inhibits TMPRSS2 protease activity and SARS-CoV-2 infection [1]
Abstract reading summary — source excerpts
- Opening excerpt
- SARS-CoV-2 is a respiratory pathogen and primarily infects the airway epithelium.
- Closing excerpt
- Our findings suggest that repurposing of α1AT-containing drugs has prospects for the therapy of COVID-19.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (152 words)
SARS-CoV-2 is a respiratory pathogen and primarily infects the airway epithelium. As our knowledge about innate immune factors of the respiratory tract against SARS-CoV-2 is limited, we generated and screened a peptide/protein library derived from bronchoalveolar lavage for inhibitors of SARS-CoV-2 spike-driven entry. Analysis of antiviral fractions revealed the presence of α1-antitrypsin (α1AT), a highly abundant circulating serine protease inhibitor. Here, we report that α1AT inhibits SARS-CoV-2 entry at physiological concentrations and suppresses viral replication in cell lines and primary cells including human airway epithelial cultures. We further demonstrate that α1AT binds and inactivates the serine protease TMPRSS2, which enzymatically primes the SARS-CoV-2 spike protein for membrane fusion. Thus, the acute phase protein α1AT is an inhibitor of TMPRSS2 and SARS-CoV-2 entry, and may play an important role in the innate immune defense against the novel coronavirus. Our findings suggest that repurposing of α1AT-containing drugs has prospects for the therapy of COVID-19.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 33741941 · DOI · PMC7979852
Alpha-1 antitrypsin deficiency: outstanding questions and future directions [2]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundAlpha-1 antitrypsin deficiency (AATD) is a rare hereditary condition that leads to decreased circulating alpha-1 antitrypsin (AAT) levels, significantly increasing the risk of serious lung and/or liver disease in children and adults, in which some aspects remain unresolved.
- Closing excerpt
- 4) Alternative strategies are currently being investigated, including the use of gene therapy or induced pluripotent stem cells, and non-augmentation strategies to prevent AAT polymerisation inside hepatocytes.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (190 words)
BackgroundAlpha-1 antitrypsin deficiency (AATD) is a rare hereditary condition that leads to decreased circulating alpha-1 antitrypsin (AAT) levels, significantly increasing the risk of serious lung and/or liver disease in children and adults, in which some aspects remain unresolved.MethodsIn this review, we summarise and update current knowledge on alpha-1 antitrypsin deficiency in order to identify and discuss areas of controversy and formulate questions that need further research.Results1) AATD is a highly underdiagnosed condition. Over 120,000 European individuals are estimated to have severe AATD and more than 90% of them are underdiagnosed.Conclusions2) Several clinical and etiological aspects of the disease are yet to be resolved. New strategies for early detection and biomarkers for patient outcome prediction are needed to reduce morbidity and mortality in these patients; 3) Augmentation therapy is the only specific approved therapy that has shown clinical efficacy in delaying the progression of emphysema. Regrettably, some countries reject registration and reimbursement for this treatment because of the lack of larger randomised, placebo-controlled trials. 4) Alternative strategies are currently being investigated, including the use of gene therapy or induced pluripotent stem cells, and non-augmentation strategies to prevent AAT polymerisation inside hepatocytes.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 29996870 · DOI · PMC6042212
Comprehensive analysis of prime editing outcomes in human embryonic stem cells [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Prime editing is a versatile and precise genome editing technique that can directly copy desired genetic modifications into target DNA sites without the need for donor DNA.
- Closing excerpt
- Our results demonstrate that prime editing in hPSCs has great potential for complementing previously developed CRISPR genome editing tools.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (173 words)
Prime editing is a versatile and precise genome editing technique that can directly copy desired genetic modifications into target DNA sites without the need for donor DNA. This technique holds great promise for the analysis of gene function, disease modeling, and the correction of pathogenic mutations in clinically relevant cells such as human pluripotent stem cells (hPSCs). Here, we comprehensively tested prime editing in hPSCs by generating a doxycycline-inducible prime editing platform. Prime editing successfully induced all types of nucleotide substitutions and small insertions and deletions, similar to observations in other human cell types. Moreover, we compared prime editing and base editing for correcting a disease-related mutation in induced pluripotent stem cells derived form a patient with α 1-antitrypsin (A1AT) deficiency. Finally, whole-genome sequencing showed that, unlike the cytidine deaminase domain of cytosine base editors, the reverse transcriptase domain of a prime editor does not lead to guide RNA-independent off-target mutations in the genome. Our results demonstrate that prime editing in hPSCs has great potential for complementing previously developed CRISPR genome editing tools.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 35018468 · DOI · PMC8789035
Circulating alpha-1 antitrypsin and its c-terminal peptides differentiate bacterial from viral community-acquired pneumonia [4]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundDistinguishing bacterial from viral community-acquired pneumonia (CAP) remains a major clinical challenge, often leading to inappropriate antimicrobial use.
- Closing excerpt
- Distinct patterns of AAT-derived peptides suggest etiology-specific proteolytic processing and merit further evaluation as markers for differentiating bacterial and viral CAP.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (173 words)
BackgroundDistinguishing bacterial from viral community-acquired pneumonia (CAP) remains a major clinical challenge, often leading to inappropriate antimicrobial use. Alpha-1 antitrypsin (AAT) is an acute-phase protein that regulates neutrophil protease activity and is cleaved during inflammation, generating bioactive peptides. We investigated whether circulating AAT and its peptides could discriminate bacterial from viral CAP.MethodsSerum samples were obtained from 81 prospectively enrolled adults with CAP (bacterial, n = 36; viral, n = 45) at hospital admission (day 0) and day 3. AAT concentrations were measured by ELISA, and nine AAT-derived C-terminal peptides were quantified by LC-MS/MS. Associations with CAP etiology were assessed using multivariable logistic regression and receiver operating characteristic (ROC) analyses.ResultsAAT concentrations were significantly higher in bacterial than viral CAP at both admission (p = 0.006) and day 3 (p ConclusionsCirculating AAT independently discriminates bacterial from viral CAP and, when combined with age and leukocyte count, show improved discriminatory performance compared with CRP-based models. Distinct patterns of AAT-derived peptides suggest etiology-specific proteolytic processing and merit further evaluation as markers for differentiating bacterial and viral CAP.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42477702 · DOI · PMC13390320
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Implications of the three-dimensional structure of alpha 1-antitrypsin for structure and function of serpins [5]
- Research article Structure and variation of human alpha 1-antitrypsin [6]
- Research article Alpha1-Antitrypsin Deficiency [7]
- Research article The discovery of α1-antitrypsin and its role in health and disease [8]
- Research article α1-Antitrypsin deficiency [9]
- Research article Clinical practice. Alpha1-antitrypsin deficiency [10]
References
- Wettstein L, Weil T, Conzelmann C, Müller JA, Groß R, Hirschenberger M, et al.. Alpha-1 antitrypsin inhibits TMPRSS2 protease activity and SARS-CoV-2 infection. . 2021. PMID 33741941 · DOI · PMC7979852
- Torres-Durán M, Lopez-Campos JL, Barrecheguren M, Miravitlles M, Martinez-Delgado B, Castillo S, et al.. Alpha-1 antitrypsin deficiency: outstanding questions and future directions. . 2018. PMID 29996870 · DOI · PMC6042212
- Habib O, Habib G, Hwang GH, Bae S. Comprehensive analysis of prime editing outcomes in human embryonic stem cells. . 2022. PMID 35018468 · DOI · PMC8789035
- Pashai Fakhri M, Börner FR, Held J, Sivaraman K, Fuge J, Rupp J, et al.. Circulating alpha-1 antitrypsin and its c-terminal peptides differentiate bacterial from viral community-acquired pneumonia. . 2026. PMID 42477702 · DOI · PMC13390320
- Huber R, Carrell RW. Implications of the three-dimensional structure of alpha 1-antitrypsin for structure and function of serpins. Biochemistry. 1989. PMID 2690952 · DOI
- Carrell RW, Jeppsson JO, Laurell CB, Brennan SO, Owen MC, Vaughan L, et al.. Structure and variation of human alpha 1-antitrypsin. Nature. 1982. PMID 7045697 · DOI
- Strnad P, McElvaney NG, Lomas DA. Alpha1-Antitrypsin Deficiency. N Engl J Med. 2020. PMID 32268028 · DOI
- Janciauskiene SM, Bals R, Koczulla R, Vogelmeier C, Köhnlein T, Welte T. The discovery of α1-antitrypsin and its role in health and disease. Respir Med. 2011. PMID 21367592 · DOI
- Greene CM, Marciniak SJ, Teckman J, Ferrarotti I, Brantly ML, Lomas DA, et al.. α1-Antitrypsin deficiency. Nat Rev Dis Primers. 2016. PMID 27465791 · DOI
- Silverman EK, Sandhaus RA. Clinical practice. Alpha1-antitrypsin deficiency. N Engl J Med. 2009. PMID 19553648 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.