Inhibition of SARS–CoV-2 by type I and type III interferons

• Published in: The Journal of biological chemistry Vol. 295; no. 41; pp. 13958 - 13964
• Main Authors: Felgenhauer, Ulrike, Schoen, Andreas, Gad, Hans Henrik, Hartmann, Rune, Schaubmar, Andreas R., Failing, Klaus, Drosten, Christian, Weber, Friedemann
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.10.2020; American Society for Biochemistry and Molecular Biology
• Subjects: Accelerated Communication; Animals; antiviral agent; Antiviral Agents - pharmacology; Betacoronavirus - drug effects; Betacoronavirus - isolation & purification; Betacoronavirus - physiology; Cell Line; Chlorocebus aethiops; Coronavirus Infections - pathology; Coronavirus Infections - virology; COVID-19; cytokine action; Humans; infection; innate immunity; interferon; Interferon Type I - pharmacology; interferon-alpha/beta; interferon-lambda; Interferons - pharmacology; Janus Kinases - metabolism; Pandemics; Pneumonia, Viral - pathology; Pneumonia, Viral - virology; Pyrazoles - pharmacology; ruxolitinib; SARS Virus - drug effects; SARS Virus - physiology; SARS-CoV-2; Signal Transduction - drug effects; Vero Cells; virology; virus; Virus Replication - drug effects; COVID-19; infection; SARS–CoV-2; innate immunity; virology; antiviral agent; interferon-alpha/beta; ruxolitinib; interferon; virus; interferon-lambda; cytokine action
• ISSN: 0021-9258; 1083-351X; 1083-351X
• DOI: 10.1074/jbc.AC120.013788

The recently emerged severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2) is the causative agent of the devastating COVID-19 lung disease pandemic. Here, we tested the inhibitory activities of the antiviral interferons of type I (IFN-α) and type III (IFN-λ) against SARS–CoV-2 and compared them with those against SARS–CoV-1, which emerged in 2003. Using two mammalian epithelial cell lines (human Calu-3 and simian Vero E6), we found that both IFNs dose-dependently inhibit SARS–CoV-2. In contrast, SARS–CoV-1 was restricted only by IFN-α in these cell lines. SARS–CoV-2 generally exhibited a broader IFN sensitivity than SARS–CoV-1. Moreover, ruxolitinib, an inhibitor of IFN-triggered Janus kinase/signal transducer and activator of transcription signaling, boosted SARS–CoV-2 replication in the IFN-competent Calu-3 cells. We conclude that SARS–CoV-2 is sensitive to exogenously added IFNs. This finding suggests that type I and especially the less adverse effect–prone type III IFN are good candidates for the management of COVID-19.