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Nafamostat-Interferon-α Combination Suppresses SARS-CoV-2 Infection In Vitro and In Vivo by Cooperatively Targeting Host TMPRSS2.
Ianevski, Aleksandr; Yao, Rouan; Lysvand, Hilde; Grødeland, Gunnveig; Legrand, Nicolas; Oksenych, Valentyn; Zusinaite, Eva; Tenson, Tanel; Bjørås, Magnar; Kainov, Denis E.
  • Ianevski A; Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway.
  • Yao R; Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway.
  • Lysvand H; Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway.
  • Grødeland G; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, 0372 Oslo, Norway.
  • Legrand N; Institute of Clinical Medicine (KlinMed), University of Oslo, 0318 Oslo, Norway.
  • Oksenych V; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, 0372 Oslo, Norway.
  • Zusinaite E; Oncodesign, 25 Avenue du Québec, 91140 Villebon Sur Yvette, France.
  • Tenson T; Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway.
  • Bjørås M; Institute of Technology, University of Tartu, 50411 Tartu, Estonia.
  • Kainov DE; Institute of Technology, University of Tartu, 50411 Tartu, Estonia.
Viruses ; 13(9)2021 09 04.
Article in English | MEDLINE | ID: covidwho-1478110
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 (IFNα) 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 IFNα and that both Serpin E1 and nafamostat 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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Benzamidines / Serine Endopeptidases / Anti-Inflammatory Agents, Non-Steroidal / Interferon-alpha / SARS-CoV-2 / COVID-19 / Guanidines Type of study: Prognostic study Topics: Vaccines / Variants Limits: Animals / Female / Humans Language: English Year: 2021 Document Type: Article Affiliation country: V13091768

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Benzamidines / Serine Endopeptidases / Anti-Inflammatory Agents, Non-Steroidal / Interferon-alpha / SARS-CoV-2 / COVID-19 / Guanidines Type of study: Prognostic study Topics: Vaccines / Variants Limits: Animals / Female / Humans Language: English Year: 2021 Document Type: Article Affiliation country: V13091768