Alpha-1 antitrypsin inhibits TMPRSS2 protease activity and SARS-CoV-2 infection.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33741941.
- Also identified by DOI 10.1038/s41467-021-21972-0 and PMC identifier 7979852.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 α<sub>1</sub>-antitrypsin (α<sub>1</sub>AT), a highly abundant circulating serine protease inhibitor. Here, we report that α<sub>1</sub>AT 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 α<sub>1</sub>AT binds and inactivates the serine protease TMPRSS2, which enzymatically primes the SARS-CoV-2 spike protein for membrane fusion. Thus, the acute phase protein α<sub>1</sub>AT 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 α<sub>1</sub>AT-containing drugs has prospects for the therapy of COVID-19.
Medical subject headings
- SARS-CoV-2
- Serine Endopeptidases
- Serine Proteinase Inhibitors
- alpha 1-Antitrypsin
- COVID-19 Drug Treatment