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

Ulrike Felgenhauer,Andreas Schoen,Hans Henrik Gad,Rune Hartmann,Andreas R Schaubmar,Klaus Failing,Christian Drosten,Friedemann Weber

doi:10.1074/jbc.ac120.013788

Abstract

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.

Highlights

The recently emerged severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2) is the causative agent of the devastating COVID-19 lung disease pandemic
We tested the effect of type I IFN against SARS–CoV-2 compared with the SARS–CoV-1 from 2003
The cells were first treated for 16 h with 100, 500, or 1000 units/ml of recombinant human IFN-a(B/D) and infected with the viruses at a multiplicity of infection (MOI) of 0.01 plaque forming units (PFU)/cell to obtain multistep growth

Summary

Introduction

The recently emerged severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2) is the causative agent of the devastating COVID-19 lung disease pandemic. Interferons of type I (IFN-a/b) and type III (IFN-l) constitute an important branch of the mammalian innate immune response These cytokines are produced by virus-infected cells and are able to establish an antiviral state in target cells by triggering the so-called JAK/STAT signaling pathway [3,4,5]. Both type I and type III IFNs are clinically used or being tested, respectively, against a range of ailments that include viral diseases [6, 7]. We investigated the potential of type I and type III IFNs against the newly emerged SARS–CoV-2

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