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Nafamostat-interferon-alpha combination suppresses SARS-CoV-2 infection in vitro and in vivo
Aleksandr Ianevski; Rouan Yo; Hilde Lysvand; Gunnveig Grodeland; Nicolas Legrand; Valentyn Oksenych; Eva Zusinaite; Tanel Tenson; Magnar Bjoras; Denis E Kainov.
Affiliation
  • Aleksandr Ianevski; NTNU
  • Rouan Yo; NTNU
  • Hilde Lysvand; NTNU
  • Gunnveig Grodeland; UiO
  • Nicolas Legrand; Oncodesign
  • Valentyn Oksenych; NTNU
  • Eva Zusinaite; University of Tartu
  • Tanel Tenson; University of Tartu
  • Magnar Bjoras; NTNU
  • Denis E Kainov; NTNU
Preprint in English | bioRxiv | ID: ppbiorxiv-448653
ABSTRACT
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.
License
cc_by_nc_nd
Full text: Available Collection: Preprints Database: bioRxiv Type of study: Prognostic study Language: English Year: 2021 Document type: Preprint
Full text: Available Collection: Preprints Database: bioRxiv Type of study: Prognostic study Language: English Year: 2021 Document type: Preprint
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