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Synergistic Interferon-Alpha-Based Combinations for Treatment of SARS-CoV-2 and Other Viral Infections.
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; Lastauskiene, Egle; Vitkauskiene, Astra; Legrand, Nicolas; Merits, Andres; Bjørås, Magnar; Kainov, Denis E.
  • Ianevski A; Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway.
  • Yao R; Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway.
  • Zusinaite E; Institute of Technology, University of Tartu, 50411 Tartu, Estonia.
  • Lello LS; Institute of Technology, University of Tartu, 50411 Tartu, Estonia.
  • Wang S; Institute of Technology, University of Tartu, 50411 Tartu, Estonia.
  • Jo E; Applied Molecular Virology Laboratory, Institut Pasteur Korea, Seongnam-si 463-400, Gyeonggi-do, Korea.
  • Yang J; Applied Molecular Virology Laboratory, Institut Pasteur Korea, Seongnam-si 463-400, Gyeonggi-do, Korea.
  • Ravlo E; Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway.
  • Wang W; Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway.
  • Lysvand H; Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway.
  • Løseth K; Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway.
  • Oksenych V; Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway.
  • Tenson T; Institute of Technology, University of Tartu, 50411 Tartu, Estonia.
  • Windisch MP; Applied Molecular Virology Laboratory, Institut Pasteur Korea, Seongnam-si 463-400, Gyeonggi-do, Korea.
  • Poranen MM; Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, 00014 Helsinki, Finland.
  • Nieminen AI; Institute for Molecular Medicine Finland, University of Helsinki, 00014 Helsinki, Finland.
  • Nordbø SA; Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway.
  • Fenstad MH; Department of Medical Microbiology, St. Olavs Hospital, 7006 Trondheim, Norway.
  • Grødeland G; Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway.
  • Aukrust P; Department of Immunology and Transfusion Medicine, St. Olavs Hospital, 7006 Trondheim, Norway.
  • Trøseid M; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, 0372 Oslo, Norway.
  • Kantele A; Institute of Clinical Medicine (KlinMed), University of Oslo, 0318 Oslo, Norway.
  • Lastauskiene E; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, 0372 Oslo, Norway.
  • Vitkauskiene A; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, 0372 Oslo, Norway.
  • Legrand N; Institute of Clinical Medicine (KlinMed), University of Oslo, 0318 Oslo, Norway.
  • Merits A; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, 0372 Oslo, Norway.
  • Bjørås M; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, 0372 Oslo, Norway.
  • Kainov DE; Institute of Clinical Medicine (KlinMed), University of Oslo, 0318 Oslo, Norway.
Viruses ; 13(12)2021 12 11.
Article in English | MEDLINE | ID: covidwho-1572663
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Interferon-alpha / SARS-CoV-2 Type of study: Prognostic study Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: V13122489

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Interferon-alpha / SARS-CoV-2 Type of study: Prognostic study Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: V13122489