Session topic


Title: Alpha-1 antitrypsin inhibits TMPRSS2 protease activity and SARS-CoV-2 infection
ID: PS 92
Type: Poster session
Talk time: 3 + 2 min
Session: Poster session 2
Antivirals and resistance I

Speaker: Lukas Wettstein (Ulm/DE)

Abstract - Text

Abstract text (incl. references and figure legends)

SARS-CoV-2 primarily infects cells of the upper and lower respiratory tract. The airway epithelium acts as a physical barrier against respiratory pathogens and its epithelial lining fluid comprises a variety of antimicrobial and antiviral compounds. To identify such compounds of the respiratory tract that inhibit SARS-CoV-2 infection, 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 by MALDI-TOF revealed the presence of α1-antitrypsin (α1AT), a highly abundant circulating serine protease inhibitor. We could show that α1AT rescues cell viability of SARS-CoV-2 infected cells and reduces size of virus induced plaques. Immunofluorescence and qPCR analysis of primary airway epithelial cells confirm that α1AT inhibits SARS-CoV-2 entry at physiological concentrations and suppresses viral replication. 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.