Other substances

Alpha-1 antitrypsin

A protease inhibitor.

Phase of research

Potential treatment - pre-clinical evidence

How it helps

Antiviral

Drug status

Used to treat other disease

Supporting references

Contradictory references

AI-suggested references

Clinical trials

General information

Alpha-1 antitrypsin is a human protein acting as a serine protease. It is active in lungs where it protects the tissue from endogenous proteases. Alpha-1 antitrypsin was also shown to inhibit TMPRSS2 and to inhibit SARS-CoV-2 cell entry and replication in vitro (Wettstein et al., 2021).

Alpha-1 antitrypsin on DrugBank
Alpha-1 antitrypsin on UniProt
Alpha-1 antitrypsin on Wikipedia

Synonyms

α1-antitrypsin; Serpin; Alpha-1-proteinase inhibitor; A1AT; α1AT; A1A; AAT; A1PI; A1AP

Marketed as

ALPHA1-PROTEINASE INHIBITOR; ARALAST; GLASSIA; PROLASTIN; RESPREEZA; ZEMAIRA

Supporting references

Link	Tested on	Impact factor	Notes	Publication date
Alpha 1 Antitrypsin is an Inhibitor of the SARS-CoV2-Priming Protease TMPRSS2 TMPRSS2 Preprint	HEK-293T cell culture		inhibitor of TMPRSS2	Oct/07/2020
Alpha-1 antitrypsin inhibits SARS-CoV-2 infection	Patients			Jul/02/2020
Alpha-1 antitrypsin inhibits TMPRSS2 protease activity and SARS-CoV-2 infection Biophysical assay Enzyme assay In vitro In silico	in silico; in vitro binding assay; in vitro enzyme assay; in vitro biophysical assay; Vero E6 and Caco-2 cells; small and human airway epithelial cells; (VSV) SARS-CoV-2 Spike pseudovirus; SARS-CoV-2 strains #014V-03890 and #010V-03903	12.12	Binds and inhibits TMPRSS2 protease. The protein inhibits SARS-CoV-2 Spike pseudovirus with an IC50 of ca. 38.5 µM in Caco-2 cells, without detectable cytotoxicity. It also inhibited two tested live virus strains in Vero E6 cells with IC50 values of 21.2 μM and 17.3 μM (similar values were also obtained for Caco-2 cells). The protease inhibitor potently reduced infection in small airway epithelial cells and human airway epithelial cells, as well.	Mar/19/2021

AI-suggested references

Link	Publication date
Is Spironolactone the Preferred Renin-Angiotensin-Aldosterone Inhibitor for Protection Against COVID-19?	Dec/04/2020
Serine Protease Inhibitors Restrict Host Susceptibility to SARS-CoV-2 Infections.	May/09/2022
Nafamostat-Interferon-alpha Combination Suppresses SARS-CoV-2 Infection In Vitro and In Vivo by Cooperatively Targeting Host TMPRSS2	Sep/04/2021
A randomized, double-blind, placebo-controlled trial of intravenous alpha-1 antitrypsin for ARDS secondary to COVID-19	Mar/11/2022
Alpha 1 Antitrypsin is an Inhibitor of the SARS-CoV-2-Priming Protease TMPRSS2.	Apr/26/2021
Repurposing proteases: An in-silico analysis of the binding potential of extracellular fungal proteases with selected viral proteins.	Jul/01/2021
Alpha-1 antitrypsin for cystic fibrosis complicated by severe cytokinemic COVID-19.	Nov/20/2020
Enoxaparin augments alpha-1-antitrypsin inhibition of TMPRSS2, a promising drug combination against COVID-19	Jul/09/2021
Using serpins cysteine protease cross-specificity to possibly trap SARS-CoV-2 Mpro with reactive center loop chimera	Feb/09/2020
Alpha-1 Antitrypsin for COVID-19 Treatment: Dual Role in Antiviral Infection and Anti-Inflammation	Dec/11/2020
Boosted Pro-Inflammatory Activity in Human PBMCs by Lipopolysaccharide and SARS-CoV-2 Spike Protein Is Regulated by alpha-1 Antitrypsin.	Jul/26/2021
Azithromycin Versus Beta-lactams in Hospitalized Patients with Acute Exacerbations of COPD	Nov/12/2020

Clinical trials

ID	Title	Status	Phase	Start date	Completion date
NCT04799873	Alpha-1-Antitrypsin-Deficiency in COVID-19	Completed		Apr/08/2020	Dec/01/2020
Alternative id - CORSAAR-AAT-001 Interventions - Drug: AAT( Alpha 1 Antitrypsin) Study type - Observational Study results - No Results Available Locations - Saarland University, Homburg, Saarland, Germany Study designs - Observational Model: Cohort\|Time Perspective: Prospective Enrollment - 10 Age - 18 Years to 110 Years (Adult, Older Adult) Outcome measures - Clinical course
NCT04675086	Aralast NP With Antiviral Treatment and Standard of Care Versus Antiviral Treatment With Standard of Care in Hospitalized Patients With Pneumonia and COVID-19 Infection	Withdrawn	Phase 3	Jan/01/2021	Dec/01/2021
Alternative id - CCR-2020-103188 Interventions - Drug: alpha1-proteinase inhibitor\|Drug: Antiviral Agents Study type - Interventional Study results - No Results Available Locations - Blessing Corporate Services, Inc, Hannibal, Missouri, United States Study designs - Allocation: Randomized\|Intervention Model: Parallel Assignment\|Masking: None (Open Label)\|Primary Purpose: Treatment Enrollment - 0 Age - 18 Years and older (Adult, Older Adult) Outcome measures - Duration of new non-invasive ventilation or high flow oxygen use (measured by days)\|Clinical status on a 7-point ordinal scale (from 1=death to 7=not hospitalized\|The percentage change in cytokine levels from screening through day 10, Day 17 and Day 24\|The percentage change in oxygen requirements including PEEP and FiO2 from screening through day 10.\|The percentage of subjects that required mechanical ventilation during the treatment period.\|The percent of patients with a SOFA score between 0-6 during treatment period.\|The percent of mortality during the treatment period.\|Evaluate the need, dosage and duration of vasopressors (number of days and average daily dose).\|Number of Days fever free (defined by temperature of <100°F (oral) for 24 hours)\|To evaluate the average number of days in the ICU\|To evaluate the average number of days in the hospital\|To evaluate the number of days with a PO2/FiO2 <300 or other parameters decided on with oxygen\|The risk of coagulopathy by measuring Prothrombin time & Partial Thromboplastin time\|The risk of coagulopathy by measuring D-Dimer\|The risk of coagulopathy by measuring Platelet Counts
NCT04547140	Study to Evaluate the Safety and Efficacy of Liquid Alpha1-Proteinase Inhibitor (Human) in Hospitalized Participants With Coronavirus Disease (COVID-19)	Recruiting	Phase 2	Jan/29/2021	Feb/01/2022
Alternative id - GC2006 Interventions - Biological: Liquid Alpha1-Proteinase Inhibitor (Human)\|Drug: Placebo\|Drug: Standard Medical Treatment Study type - Interventional Study results - No Results Available Locations - Birmingham VA, Birmingham, Alabama, United States\|St. Joseph's Hospital, Phoenix, Arizona, United States\|University of Miami Hospital, Miami, Florida, United States\|Sparrow Hospital, Lansing, Michigan, United States\|Hannibal Clinic, Hannibal, Missouri, United States\|Kansas City VA, Kansas City, Missouri, United States\|CHI Health Center, Omaha, Nebraska, United States\|Columbia University Medical Center, New York, New York, United States\|Temple University Hospital, Philadelphia, Pennsylvania, United States\|Memphis VA, Memphis, Tennessee, United States\|University of Utah, Salt Lake City, Utah, United States\|MultiCare Tacoma General Hospital, Tacoma, Washington, United States\|AngioCor Blumenau, Blumenau, Santa Catarina, Brazil\|Hospital Sao Jose, Criciúma, Santa Catarina, Brazil\|Hospital das Clinicas da Faculdade de Medicina de Botucatu, Botucatu, São Paulo, Brazil\|Hospital Dia do Pulmão, Blumenau, Brazil\|Hospital Alemao Oswaldo Cruz, São Paulo, Brazil\|Universidade Federal de Sao Paulo, São Paulo, Brazil\|Hospital Padre Hurtado, Santiago, Chile\|Hospital Carlos Van Buren, Valparaíso, Chile\|Fundación Oftalmológica de Santander, Bucaramanga, Santander, Colombia\|Unidad Medica para la Salud Integral, San Nicolás de los Garza, Mexico Study designs - Allocation: Randomized\|Intervention Model: Parallel Assignment\|Masking: Double (Participant, Investigator)\|Primary Purpose: Treatment Enrollment - 100 Age - 18 Years and older (Adult, Older Adult) Outcome measures - Percentage of Participants Dying or Requiring ICU Admission\|Percentage of Participants Who are Dependent on High Flow Oxygen Devices or Invasive Mechanical Ventilation\|Change from Baseline in National Early Warning Score (NEWS)\|Time to Clinical Response as Assessed by: NEWS ≤ 2 Maintained for 24 hours\|Time to Hospital Discharge\|Duration of ICU Stay\|Duration of Any Oxygen Use\|Duration of Mechanical Ventilation\|Mean Change from Baseline in Ordinal Scale\|Absolute Value Change from Baseline in Ordinal Scale\|Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale\|Time to Sustained Normalization of Temperature\|Percentage of Participants with Normalization of Fever\|Number of Participants who Develop Acute Respiratory Distress Syndrome (ARDS)\|Length of Time to Clinical Progression
NCT04495101	Study to Evaluate the Safety and Efficacy of Prolastin in Hospitalized Subjects With COVID-19	Completed	Phase 2	Jul/29/2020	Jun/10/2021
Alternative id - GC2005\|2020-001953-36 Interventions - Biological: Prolastin\|Drug: Standard Medical Treatment Study type - Interventional Study results - No Results Available Locations - Hospital Universitario de Burgos, Burgos, Castilla León, Spain\|Hospital Universitari Germans Trias i Pujol, Badalona, Spain\|Hospital Clínic de Barcelona, Barcelona, Spain\|Hospital Universitario Valle de Hebrón, Barcelona, Spain\|Hospital Clínico San Carlos, Madrid, Spain\|Hospital General Gregorio Marañón, Madrid, Spain\|Hospital Universitario Infanta Leonor, Madrid, Spain\|Hospital Universitario Príncipe de Asturias, Madrid, Spain\|Hospital Universitario Ramón y Cajal, Madrid, Spain Study designs - Allocation: Randomized\|Intervention Model: Parallel Assignment\|Masking: None (Open Label)\|Primary Purpose: Treatment Enrollment - 100 Age - 18 Years and older (Adult, Older Adult) Outcome measures - Percentage of Subjects Dying or Requiring ICU Admission\|Percentage of Subjects Who are Dependent on Invasive Mechanical Ventilation\|Change from Baseline in National Early Warning Score (NEWS)\|Time to Clinical Response as Assessed by: NEWS ≤ 2 Maintained for 24 hours\|Time to Hospital Discharge\|Duration of ICU Stay\|Duration of Any Oxygen Use\|Duration of Mechanical Ventilation\|Mean Change from Baseline in Ordinal Scale\|Absolute Value Change from Baseline in Ordinal Scale\|Percentage of Subjects in Each Severity Category of the 7-Point Ordinal Scale\|Time to Sustained Normalization of Temperature\|Percentage of Subjects who Sustained Normalization of Temperature\|Number of Subjects who Develop Acute Respiratory Distress Syndrome (ARDS)\|Length of Time to Clinical Progression\|Mortality Through Day 29

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