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

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 i...

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Autores principales: Ianevski, Aleksandr, Yao, Rouan, Lysvand, Hilde, Grødeland, Gunnveig, Legrand, Nicolas, Oksenych, Valentyn, Zusinaite, Eva, Tenson, Tanel, Bjørås, Magnar, Kainov, Denis E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473362/
https://www.ncbi.nlm.nih.gov/pubmed/34578348
http://dx.doi.org/10.3390/v13091768
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author Ianevski, Aleksandr
Yao, Rouan
Lysvand, Hilde
Grødeland, Gunnveig
Legrand, Nicolas
Oksenych, Valentyn
Zusinaite, Eva
Tenson, Tanel
Bjørås, Magnar
Kainov, Denis E.
author_facet Ianevski, Aleksandr
Yao, Rouan
Lysvand, Hilde
Grødeland, Gunnveig
Legrand, Nicolas
Oksenych, Valentyn
Zusinaite, Eva
Tenson, Tanel
Bjørås, Magnar
Kainov, Denis E.
author_sort Ianevski, Aleksandr
collection PubMed
description 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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spelling pubmed-84733622021-09-28 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. Viruses Brief Report 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. MDPI 2021-09-04 /pmc/articles/PMC8473362/ /pubmed/34578348 http://dx.doi.org/10.3390/v13091768 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Ianevski, Aleksandr
Yao, Rouan
Lysvand, Hilde
Grødeland, Gunnveig
Legrand, Nicolas
Oksenych, Valentyn
Zusinaite, Eva
Tenson, Tanel
Bjørås, Magnar
Kainov, Denis E.
Nafamostat–Interferon-α Combination Suppresses SARS-CoV-2 Infection In Vitro and In Vivo by Cooperatively Targeting Host TMPRSS2
title Nafamostat–Interferon-α Combination Suppresses SARS-CoV-2 Infection In Vitro and In Vivo by Cooperatively Targeting Host TMPRSS2
title_full Nafamostat–Interferon-α Combination Suppresses SARS-CoV-2 Infection In Vitro and In Vivo by Cooperatively Targeting Host TMPRSS2
title_fullStr Nafamostat–Interferon-α Combination Suppresses SARS-CoV-2 Infection In Vitro and In Vivo by Cooperatively Targeting Host TMPRSS2
title_full_unstemmed Nafamostat–Interferon-α Combination Suppresses SARS-CoV-2 Infection In Vitro and In Vivo by Cooperatively Targeting Host TMPRSS2
title_short Nafamostat–Interferon-α Combination Suppresses SARS-CoV-2 Infection In Vitro and In Vivo by Cooperatively Targeting Host TMPRSS2
title_sort nafamostat–interferon-α combination suppresses sars-cov-2 infection in vitro and in vivo by cooperatively targeting host tmprss2
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473362/
https://www.ncbi.nlm.nih.gov/pubmed/34578348
http://dx.doi.org/10.3390/v13091768
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