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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8473362 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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