Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jun 8;14(6):1247.
doi: 10.3390/v14061247.

Characterization of SARS-CoV-2 Evasion: Interferon Pathway and Therapeutic Options

Mariem Znaidia  1 , Caroline Demeret  1 , Sylvie van der Werf  1 , Anastassia V Komarova  1
Affiliations
Review

Characterization of SARS-CoV-2 Evasion: Interferon Pathway and Therapeutic Options

Mariem Znaidia et al. Viruses. .

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. SARS-CoV-2 is characterized by an important capacity to circumvent the innate immune response. The early interferon (IFN) response is necessary to establish a robust antiviral state. However, this response is weak and delayed in COVID-19 patients, along with massive pro-inflammatory cytokine production. This dysregulated innate immune response contributes to pathogenicity and in some individuals leads to a critical state. Characterizing the interplay between viral factors and host innate immunity is crucial to better understand how to manage the disease. Moreover, the constant emergence of new SARS-CoV-2 variants challenges the efficacy of existing vaccines. Thus, to control this virus and readjust the antiviral therapy currently used to treat COVID-19, studies should constantly be re-evaluated to further decipher the mechanisms leading to SARS-CoV-2 pathogenesis. Regarding the role of the IFN response in SARS-CoV-2 infection, in this review we summarize the mechanisms by which SARS-CoV-2 evades innate immune recognition. More specifically, we explain how this virus inhibits IFN signaling pathways (IFN-I/IFN-III) and controls interferon-stimulated gene (ISG) expression. We also discuss the development and use of IFNs and potential drugs controlling the innate immune response to SARS-CoV-2, helping to clear the infection.

Keywords: SARS-CoV-2; antagonism; innate immunity; interferon; therapy; virus–host interactions.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Model describing the pathways targeted by SARS-CoV-2 to antagonize the innate immune response.
See this image and copyright information in PMC

References

    1. Wu F., Zhao S., Yu B., Chen Y.-M., Wang W., Song Z.-G., Hu Y., Tao Z.-W., Tian J.-H., Pei Y.-Y., et al. A New Coronavirus Associated with Human Respiratory Disease in China. Nature. 2020;579:265–269. doi: 10.1038/s41586-020-2008-3. - DOI - PMC - PubMed
    1. Khailany R.A., Safdar M., Ozaslan M. Genomic Characterization of a Novel SARS-CoV-2. Gene Rep. 2020;19:100682. doi: 10.1016/j.genrep.2020.100682. - DOI - PMC - PubMed
    1. Malone B., Urakova N., Snijder E.J., Campbell E.A. Structures and Functions of Coronavirus Replication–Transcription Complexes and Their Relevance for SARS-CoV-2 Drug Design. Nat. Rev. Mol. Cell Biol. 2022;23:21–39. doi: 10.1038/s41580-021-00432-z. - DOI - PMC - PubMed
    1. Davidson A.D., Williamson M.K., Lewis S., Shoemark D., Carroll M.W., Heesom K.J., Zambon M., Ellis J., Lewis P.A., Hiscox J.A., et al. Characterisation of the Transcriptome and Proteome of SARS-CoV-2 Reveals a Cell Passage Induced in-Frame Deletion of the Furin-like Cleavage Site from the Spike Glycoprotein. Genome Med. 2020;12:68. doi: 10.1186/s13073-020-00763-0. - DOI - PMC - PubMed
    1. Kim D., Lee J.-Y., Yang J.-S., Kim J.W., Kim V.N., Chang H. The Architecture of SARS-CoV-2 Transcriptome. Cell. 2020;181:914–921.e10. doi: 10.1016/j.cell.2020.04.011. - DOI - PMC - PubMed

Publication types

Supplementary concepts

LinkOut - more resources