Activation of STING signaling pathway effectively blocks human coronavirus infection

Wei Liu, Hanako M. Reyes, June F. Yang, Yize Li, Kathleen M. Stewart, Maria C. Basil, Susan M. Lin, Jeremy Katzen, Edward E. Morrisey, Susan R. Weiss, Jianxin You

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The COVID-19 pandemic poses a serious global health threat. The rapid global spread of SARS-CoV-2 highlights an urgent need to develop effective therapeutics for blocking SARS-CoV-2 infection and spread. Stimulator of Interferon Genes (STING) is a chief element in host antiviral defense pathways. In this study, we examined the impact of the STING signaling pathway on coronavirus infection using the human coronavirus OC43 (HCoV-OC43) model. We found that HCoV-OC43 infection did not stimulate the STING signaling pathway, but the activation of STING signaling effectively inhibits HCoV-OC43 infection to a much greater extent than that of type I interferons (IFNs). We also discovered that IRF3, the key STING downstream innate immune effector, is essential for this anticoronavirus activity. In addition, we found that the amidobenzimidazole (ABZI)-based human STING agonist diABZI robustly blocks the infection of not only HCoV-OC43 but also SARS-CoV-2. Therefore, our study identifies the STING signaling pathway as a potential therapeutic target that could be exploited for developing broad-spectrum antiviral therapeutics against multiple coronavirus strains in order to face the challenge of future coronavirus outbreaks. IMPORTANCE The highly infectious and lethal SARS-CoV-2 is posing an unprecedented threat to public health. Other coronaviruses are likely to jump from a nonhuman animal to humans in the future. Novel broad-spectrum antiviral therapeutics are therefore needed to control known pathogenic coronaviruses such as SARS-CoV-2 and its newly mutated variants, as well as future coronavirus outbreaks. STING signaling is a well-established host defense pathway, but its role in coronavirus infection remains unclear. In the present study, we found that activation of the STING signaling pathway robustly inhibits infection of HCoV-OC43 and SARS-CoV-2. These results identified the STING pathway as a novel target for controlling the spread of known pathogenic coronaviruses, as well as emerging coronavirus outbreaks.

Original languageEnglish (US)
Article numbere00490
JournalJournal of virology
Volume95
Issue number12
DOIs
StatePublished - Jun 2021
Externally publishedYes

Keywords

  • Antiviral therapy
  • Coronavirus
  • COVID-19
  • HCoV-OC43
  • SARS-CoV-2
  • STING

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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