Viruses (Dec 2021)
Synergistic Interferon-Alpha-Based Combinations for Treatment of SARS-CoV-2 and Other Viral Infections
- Aleksandr Ianevski,
- Rouan Yao,
- Eva Zusinaite,
- Laura Sandra Lello,
- Sainan Wang,
- Eunji Jo,
- Jaewon Yang,
- Erlend Ravlo,
- Wei Wang,
- Hilde Lysvand,
- Kirsti Løseth,
- Valentyn Oksenych,
- Tanel Tenson,
- Marc P. Windisch,
- Minna M. Poranen,
- Anni I. Nieminen,
- Svein Arne Nordbø,
- Mona Høysæter Fenstad,
- Gunnveig Grødeland,
- Pål Aukrust,
- Marius Trøseid,
- Anu Kantele,
- Eglė Lastauskienė,
- Astra Vitkauskienė,
- Nicolas Legrand,
- Andres Merits,
- Magnar Bjørås,
- Denis E. Kainov
Affiliations
- Aleksandr Ianevski
- Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway
- Rouan Yao
- Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway
- Eva Zusinaite
- Institute of Technology, University of Tartu, 50411 Tartu, Estonia
- Laura Sandra Lello
- Institute of Technology, University of Tartu, 50411 Tartu, Estonia
- Sainan Wang
- Institute of Technology, University of Tartu, 50411 Tartu, Estonia
- Eunji Jo
- Applied Molecular Virology Laboratory, Institut Pasteur Korea, Seongnam-si 463-400, Gyeonggi-do, Korea
- Jaewon Yang
- Applied Molecular Virology Laboratory, Institut Pasteur Korea, Seongnam-si 463-400, Gyeonggi-do, Korea
- Erlend Ravlo
- Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway
- Wei Wang
- Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway
- Hilde Lysvand
- Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway
- Kirsti Løseth
- Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway
- Valentyn Oksenych
- Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway
- Tanel Tenson
- Institute of Technology, University of Tartu, 50411 Tartu, Estonia
- Marc P. Windisch
- Applied Molecular Virology Laboratory, Institut Pasteur Korea, Seongnam-si 463-400, Gyeonggi-do, Korea
- Minna M. Poranen
- Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, 00014 Helsinki, Finland
- Anni I. Nieminen
- Institute for Molecular Medicine Finland, University of Helsinki, 00014 Helsinki, Finland
- Svein Arne Nordbø
- Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway
- Mona Høysæter Fenstad
- Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway
- Gunnveig Grødeland
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, 0372 Oslo, Norway
- Pål Aukrust
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, 0372 Oslo, Norway
- Marius Trøseid
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, 0372 Oslo, Norway
- Anu Kantele
- Inflammation Center, Infectious Diseases, Helsinki University Hospital, 00029 Helsinki, Finland
- Eglė Lastauskienė
- Life Sciences Center, Vilnius University, 10257 Vilnius, Lithuania
- Astra Vitkauskienė
- Department of Laboratory Medicine, Lithuanian University of Health Science, 44307 Kaunas, Lithuania
- Nicolas Legrand
- Oncodesign, 25 Avenue du Québec, 91140 Villebon Sur Yvette, France
- Andres Merits
- Institute of Technology, University of Tartu, 50411 Tartu, Estonia
- Magnar Bjørås
- Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway
- Denis E. Kainov
- Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway
- DOI
- https://doi.org/10.3390/v13122489
- Journal volume & issue
-
Vol. 13,
no. 12
p. 2489
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
- interferon-alpha
- antiviral drug combination
- SARS-CoV-2
- hepatitis C virus
- hepatitis E virus
- influenza A virus
