{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:15:10Z","timestamp":1787030110924,"version":"build-2736575974"},"reference-count":71,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,11]],"date-time":"2021-12-11T00:00:00Z","timestamp":1639180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002301","name":"Estonian Research Council","doi-asserted-by":"publisher","award":["MOBTT39"],"award-info":[{"award-number":["MOBTT39"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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), IFN\u03b1, in combination with remdesivir, EIDD-2801, camostat, cycloheximide, or convalescent serum, proved to be more effective. Transcriptome and metabolomic analyses revealed that the IFN\u03b1\u2013remdesivir 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 IFN\u03b1 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 IFN\u03b1 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.<\/jats:p>","DOI":"10.3390\/v13122489","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T03:14:29Z","timestamp":1639365269000},"page":"2489","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Synergistic Interferon-Alpha-Based Combinations for Treatment of SARS-CoV-2 and Other Viral Infections"],"prefix":"10.3390","volume":"13","author":[{"given":"Aleksandr","family":"Ianevski","sequence":"first","affiliation":[{"name":"Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rouan","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Zusinaite","sequence":"additional","affiliation":[{"name":"Institute of Technology, University of Tartu, 50411 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Sandra","family":"Lello","sequence":"additional","affiliation":[{"name":"Institute of Technology, University of Tartu, 50411 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sainan","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Technology, University of Tartu, 50411 Tartu, 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Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,11]]},"reference":[{"key":"ref_1","first-page":"493","article-title":"Antiviral activity of cepharanthine against severe acute respiratory syndrome coronavirus in vitro","volume":"118","author":"Zhang","year":"2005","journal-title":"Chin. 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