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