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

Authors :
Aleksandr Ianevski
Rouan Yao
Hilde Lysvand
Gunnveig Grødeland
Nicolas Legrand
Valentyn Oksenych
Eva Zusinaite
Tanel Tenson
Magnar Bjørås
Denis E. Kainov
Source :
Viruses, Vol 13, Iss 9, p 1768 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

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.

Details

Language :
English
ISSN :
19994915
Volume :
13
Issue :
9
Database :
Directory of Open Access Journals
Journal :
Viruses
Publication Type :
Academic Journal
Accession number :
edsdoj.228754c4800149fb83c6624dc0ae3929
Document Type :
article
Full Text :
https://doi.org/10.3390/v13091768