Serine Protease Inhibitors Restrict Host Susceptibility to SARS-CoV-2 Infections
Ebba Rosendal, Ionut Sebastian Mihai, Miriam Becker, Debojyoti Das, Lars Frängsmyr, B. David Persson, Gregory Rankin, Remigius Gröning, Johan Trygg, Mattias N.E. Forsell, Johan Ankarklev, Anders Blomberg, Johan Henriksson, Anna K. Överby, Annasara Lenman
Abstract
Identification of host factors affecting individual SARS-CoV-2 susceptibility will provide a better understanding of the large variations in disease severity and will identify potential factors that can be used, or targeted, in antiviral drug development. With the use of an advanced lung cell model established from several human donors, we identified cellular protease inhibitors, serpins, as host factors that restrict SARS-CoV-2 infection. The antiviral mechanism was found to be mediated by the inhibition of a serine protease, TMPRSS2, which results in a blockage of viral entry into target cells. Potential treatments with these serpins would not only reduce the overall viral burden in the patients, but also block the infection at an early time point, reducing the risk for the hyperactive immune response common in patients with severe COVID-19.