Viruses · 2021
Synergistic Interferon-Alpha-Based Combinations for Treatment of SARS-CoV-2 and Other Viral Infections.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Ianevski Aleksandr, Yao Rouan, Zusinaite Eva, Lello Laura Sandra, Wang Sainan, Jo Eunji, Yang Jaewon, Ravlo Erlend, Wang Wei, Lysvand Hilde, Løseth Kirsti, Oksenych Valentyn, Tenson Tanel, Windisch Marc P, Poranen Minna M, Nieminen Anni I, Nordbø Svein Arne, Fenstad Mona Høysæter, Grødeland Gunnveig, Aukrust Pål, Trøseid Marius, Kantele Anu, Lastauskienė Eglė, Vitkauskienė Astra, Legrand Nicolas, Merits Andres, Bjørås Magnar, Kainov Denis E
Аннотация
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.
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.