RT Journal Article SR Electronic T1 Nafamostat-interferon-alpha combination suppresses SARS-CoV-2 infection in vitro and in vivo JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.06.16.448653 DO 10.1101/2021.06.16.448653 A1 Aleksandr Ianevski A1 Rouan Yao A1 Hilde Lysvand A1 Gunnveig Grødeland A1 Nicolas Legrand A1 Tanel Tenson A1 Magnar Bjørås A1 Denis E. Kainov YR 2021 UL http://biorxiv.org/content/early/2021/06/16/2021.06.16.448653.abstract AB SARS-CoV-2 and its vaccine/immune-escaping variants continue to pose a serious threat to public health due to a paucity of effective, rapidly deployable, and widely available treatments. Here we address these challenges by combining Pegasys (IFNa) and nafamostat to effectively suppress SARS-CoV-2 infection in cell culture and hamsters. Our results indicate that Serpin E1 is an important mediator of the antiviral activity of IFNa and that both Serpin E1 and camostat can target the same cellular factor TMPRSS2, which plays a critical role in viral replication. The low doses of the drugs in combination may have several clinical advantages, including fewer adverse events and improved patient outcome. Thus, our study may provide a proactive solution for the ongoing pandemic and potential future coronavirus outbreaks, which is still urgently required in many parts of the world.Competing Interest StatementThe authors have declared no competing interest.