Your browser doesn't support javascript.
Alpha-1 antitrypsin inhibits TMPRSS2 protease activity and SARS-CoV-2 infection.
Wettstein, Lukas; Weil, Tatjana; Conzelmann, Carina; Müller, Janis A; Groß, Rüdiger; Hirschenberger, Maximilian; Seidel, Alina; Klute, Susanne; Zech, Fabian; Prelli Bozzo, Caterina; Preising, Nico; Fois, Giorgio; Lochbaum, Robin; Knaff, Philip Maximilian; Mailänder, Volker; Ständker, Ludger; Thal, Dietmar Rudolf; Schumann, Christian; Stenger, Steffen; Kleger, Alexander; Lochnit, Günter; Mayer, Benjamin; Ruiz-Blanco, Yasser B; Hoffmann, Markus; Sparrer, Konstantin M J; Pöhlmann, Stefan; Sanchez-Garcia, Elsa; Kirchhoff, Frank; Frick, Manfred; Münch, Jan.
  • Wettstein L; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Weil T; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Conzelmann C; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Müller JA; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Groß R; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Hirschenberger M; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Seidel A; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Klute S; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Zech F; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Prelli Bozzo C; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Preising N; Core Facility Functional Peptidomics, Ulm University Medical Center, Ulm, Germany.
  • Fois G; Institute of General Physiology, Ulm University, Ulm, Germany.
  • Lochbaum R; Institute of General Physiology, Ulm University, Ulm, Germany.
  • Knaff PM; Dermatology Clinic, University Medicine Mainz, Mainz, Germany.
  • Mailänder V; Max-Planck-Institute for Polymer Research, Mainz, Germany.
  • Ständker L; Dermatology Clinic, University Medicine Mainz, Mainz, Germany.
  • Thal DR; Max-Planck-Institute for Polymer Research, Mainz, Germany.
  • Schumann C; Core Facility Functional Peptidomics, Ulm University Medical Center, Ulm, Germany.
  • Stenger S; Laboratory of Neuropathology, Department of Imaging and Pathology, KU-Leuven and Department of Pathology, UZ-Leuven, Leuven, Belgium.
  • Kleger A; Laboratory of Neuropathology, Institute of Pathology, Ulm University, Ulm, Germany.
  • Lochnit G; Pneumology, Thoracic Oncology, Sleep and Respiratory Critical Care Medicine, Clinics Allgäu, Kempten and Immenstadt, Germany.
  • Mayer B; Institute for Microbiology and Hygiene, Ulm University Medical Center, Ulm, Germany.
  • Ruiz-Blanco YB; Department of Internal Medicine 1, Ulm University Hospital, Ulm, Germany.
  • Hoffmann M; Institute of Biochemistry, Justus-Liebig University Giessen, Giessen, Germany.
  • Sparrer KMJ; Institute for Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.
  • Pöhlmann S; Computational Biochemistry, Center of Medical Biotechnology, University of Duisburg-Essen, Essen, Germany.
  • Sanchez-Garcia E; Infection Biology Unit, German Primate Center- Leibniz institute for Primate Research, Göttingen, Germany.
  • Kirchhoff F; Faculty of Biology and Psychology, Georg-August-University, Göttingen, Germany.
  • Frick M; Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • Münch J; Infection Biology Unit, German Primate Center- Leibniz institute for Primate Research, Göttingen, Germany.
Nat Commun ; 12(1): 1726, 2021 03 19.
Article in English | MEDLINE | ID: covidwho-1142436
Semantic information from SemMedBD (by NLM)
1. alpha 1-antitrypsin DISRUPTS peptidase activity
Subject
alpha 1-antitrypsin
Predicate
DISRUPTS
Object
peptidase activity
2. Inhibitor PART_OF TMPRSS2 gene|TMPRSS2
Subject
Inhibitor
Predicate
PART_OF
Object
TMPRSS2 gene|TMPRSS2
3. Pharmaceutical Preparations TREATS COVID-19
Subject
Pharmaceutical Preparations
Predicate
TREATS
Object
COVID-19
4. alpha 1-antitrypsin DISRUPTS peptidase activity
Subject
alpha 1-antitrypsin
Predicate
DISRUPTS
Object
peptidase activity
5. Inhibitor PART_OF TMPRSS2 gene|TMPRSS2
Subject
Inhibitor
Predicate
PART_OF
Object
TMPRSS2 gene|TMPRSS2
6. Pharmaceutical Preparations TREATS COVID-19
Subject
Pharmaceutical Preparations
Predicate
TREATS
Object
COVID-19
ABSTRACT
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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Serine Endopeptidases / Serine Proteinase Inhibitors / Alpha 1-Antitrypsin / SARS-CoV-2 / COVID-19 Limits: Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-21972-0

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Serine Endopeptidases / Serine Proteinase Inhibitors / Alpha 1-Antitrypsin / SARS-CoV-2 / COVID-19 Limits: Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-21972-0