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Brief Report

Nafamostat–Interferon-α Combination Suppresses SARS-CoV-2 Infection In Vitro and In Vivo by Cooperatively Targeting Host TMPRSS2

1
Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway
2
Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, 0372 Oslo, Norway
3
Institute of Clinical Medicine (KlinMed), University of Oslo, 0318 Oslo, Norway
4
Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, 0372 Oslo, Norway
5
Oncodesign, 25 Avenue du Québec, 91140 Villebon Sur Yvette, France
6
Institute of Technology, University of Tartu, 50411 Tartu, Estonia
7
Institute for Molecular Medicine Finland, FIMM, University of Helsinki, 00014 Helsinki, Finland
*
Authors to whom correspondence should be addressed.
Academic Editor: Caijun Sun
Viruses 2021, 13(9), 1768; https://doi.org/10.3390/v13091768
Received: 10 August 2021 / Revised: 31 August 2021 / Accepted: 3 September 2021 / Published: 4 September 2021
(This article belongs to the Special Issue Broad Spectrum Antivirals and Antiviral Combinations)
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. View Full-Text
Keywords: SARS-CoV-2; interferon-alpha; nafamostat; antiviral drug combination; broad-spectrum antivirals SARS-CoV-2; interferon-alpha; nafamostat; antiviral drug combination; broad-spectrum antivirals
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MDPI and ACS Style

Ianevski, A.; Yao, R.; Lysvand, H.; Grødeland, G.; Legrand, N.; Oksenych, V.; Zusinaite, E.; Tenson, T.; Bjørås, M.; Kainov, D.E. Nafamostat–Interferon-α Combination Suppresses SARS-CoV-2 Infection In Vitro and In Vivo by Cooperatively Targeting Host TMPRSS2. Viruses 2021, 13, 1768. https://doi.org/10.3390/v13091768

AMA Style

Ianevski A, Yao R, Lysvand H, Grødeland G, Legrand N, Oksenych V, Zusinaite E, Tenson T, Bjørås M, Kainov DE. Nafamostat–Interferon-α Combination Suppresses SARS-CoV-2 Infection In Vitro and In Vivo by Cooperatively Targeting Host TMPRSS2. Viruses. 2021; 13(9):1768. https://doi.org/10.3390/v13091768

Chicago/Turabian Style

Ianevski, Aleksandr, Rouan Yao, Hilde Lysvand, Gunnveig Grødeland, Nicolas Legrand, Valentyn Oksenych, Eva Zusinaite, Tanel Tenson, Magnar Bjørås, and Denis E. Kainov. 2021. "Nafamostat–Interferon-α Combination Suppresses SARS-CoV-2 Infection In Vitro and In Vivo by Cooperatively Targeting Host TMPRSS2" Viruses 13, no. 9: 1768. https://doi.org/10.3390/v13091768

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