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Viruses
. 2021 Dec 11;13(12):2489.
doi: 10.3390/v13122489.
Synergistic Interferon-Alpha-Based Combinations for Treatment of SARS-CoV-2 and Other Viral Infections
Aleksandr Ianevski 1 , Rouan Yao 1 , Eva Zusinaite 2 , Laura Sandra Lello 2 , Sainan Wang 2 , Eunji Jo 3 , Jaewon Yang 3 , Erlend Ravlo 1 , Wei Wang 1 , Hilde Lysvand 1 , Kirsti Løseth 1 , Valentyn Oksenych 1 , Tanel Tenson 2 , Marc P Windisch 3 , Minna M Poranen 4 , Anni I Nieminen 5 , Svein Arne Nordbø 1 6 , Mona Høysæter Fenstad 1 7 , Gunnveig Grødeland 8 9 10 , Pål Aukrust 8 9 10 , Marius Trøseid 8 9 10 , Anu Kantele 11 , Eglė Lastauskienė 12 , Astra Vitkauskienė 13 , Nicolas Legrand 14 , Andres Merits 2 , Magnar Bjørås 1 , Denis E Kainov 1 2 5
Affiliations
- PMID: 34960758
- DOI: 10.3390/v13122489
Abstract
Background: There is an urgent need for new antivirals with powerful therapeutic potential and tolerable side effects.
Methods: Here, we tested the antiviral properties of interferons (IFNs), alone and with other drugs in vitro.
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.
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.
Keywords: SARS-CoV-2; antiviral drug combination; hepatitis C virus; hepatitis E virus; human immunodeficiency virus; influenza A virus; interferon-alpha.