Alpha-1 antitrypsin inhibits SARS-CoV-2 infection

Wettstein, Lukas; Conzelmann, Carina; Müller, Janis A.; Weil, Tatjana; Groß, Rüdiger; Hirschenberger, Maximilian; Seidel, Alina; Klute, Susanne; Zech, Fabian; Bozzo, Caterina Prelli; Preising, Nico; Fois, Giorgio; Lochbaum, Robin; Knaff, Philip; Mailänder, Volker; Ständker, Ludger; Thal, Dietmar Rudolf; Schumann, Christian; Stenger, Steffen; Kleger, Alexander; Lochnit, Günter; Sparrer, Konstantin; Kirchhoff, Frank; Frick, Manfred; Münch, Jan

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). To identify factors of the respiratory tract that suppress SARS-CoV-2, we screened a peptide/protein library derived from bronchoalveolar lavage, and identified α1-antitrypsin (α1-AT) as specific inhibitor of SARS-CoV-2. α1-AT targets the viral spike protein and blocks SARS-CoV-2 infection of human airway epithelium at physiological concentrations. Our findings show that endogenous α1-AT restricts SARS-CoV-2 and repurposes α1-AT-based drugs for COVID-19 therapy.