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.
【저자키워드】 SARS-CoV-2, interferon-alpha, influenza A virus, hepatitis C virus, antiviral drug combination, Human immunodeficiency virus, hepatitis E virus, 【초록키워드】 HIV, coronavirus, Antiviral, Transcription, interferon, Remdesivir, drug, in vitro, ribavirin, viral infections, HCV, Replication, IFN, EIDD-2801, target, lung organoids, Viral RNA, organoids, Side effects, Calu-3 cell, convalescent serum, homeostasis, IFNs, IFNα, Combination, Analysis, protein synthesis, antiviral property, acute respiratory syndrome, cycloheximide, therapeutic potential, clinical development, while, Affect, metabolomic, effective, concentrations, synergistic, tested, indicated, changes in, demonstrated, suppressed, NITD008, tolerable, uninfected cell, 【제목키워드】 Other,