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Synergistic Interferon-Alpha-Based Combinations for Treatment of SARS-CoV-2 and Other Viral Infections.
- Source :
-
Viruses [Viruses] 2021 Dec 11; Vol. 13 (12). Date of Electronic Publication: 2021 Dec 11. - Publication Year :
- 2021
-
Abstract
- Background: There is an urgent need for new antivirals with powerful therapeutic potential and tolerable side effects.<br />Methods: Here, we tested the antiviral properties of interferons (IFNs), alone and with other drugs in vitro.<br />Results: While IFNs alone were insufficient to completely abolish replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), IFNα, in combination with remdesivir, EIDD-2801, camostat, cycloheximide, or convalescent serum, proved to be more effective. Transcriptome and metabolomic analyses revealed that the IFNα-remdesivir combination suppressed SARS-CoV-2-mediated changes in Calu-3 cells and lung organoids, although it altered the homeostasis of uninfected cells and organoids. We also demonstrated that IFNα combinations with sofosbuvir, telaprevir, NITD008, ribavirin, pimodivir, or lamivudine were effective against HCV, HEV, FLuAV, or HIV at lower concentrations, compared to monotherapies.<br />Conclusions: Altogether, our results indicated that IFNα can be combined with drugs that affect viral RNA transcription, protein synthesis, and processing to make synergistic combinations that can be attractive targets for further pre-clinical and clinical development against emerging and re-emerging viral infections.
- Subjects :
- Cell Line
Drug Synergism
Humans
Lung drug effects
Lung metabolism
Lung virology
Metabolome drug effects
Organoids
RNA, Viral biosynthesis
RNA, Viral drug effects
Signal Transduction drug effects
Transcriptome drug effects
Virus Replication drug effects
Viruses classification
Viruses drug effects
Antiviral Agents pharmacology
Interferon-alpha pharmacology
SARS-CoV-2 drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1999-4915
- Volume :
- 13
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Viruses
- Publication Type :
- Academic Journal
- Accession number :
- 34960758
- Full Text :
- https://doi.org/10.3390/v13122489