Title Synergistic interferon-alpha-based combinations for treatment of SARS-CoV-2 and other viral infections /
Authors 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
DOI 10.3390/v13122489
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Is Part of Viruses.. Basel : MDPI AG. 2021, vol. 13, iss. 12, art. no. 2489, p. [1-18].. eISSN 1999-4915
Keywords [eng] interferon-alpha ; antiviral drug combination ; SARS-CoV-2 ; hepatitis C virus ; hepatitis E virus ; influenza A virus ; human immunodeficiency virus
Abstract [eng] 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.
Published Basel : MDPI AG
Type Journal article
Language English
Publication date 2021
CC license CC license description