期刊
JOURNAL OF VIROLOGY
卷 95, 期 12, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00490-21
关键词
HCoV-OC43; SARS-CoV-2; COVID-19; coronavirus; STING; antiviral therapy
类别
资金
- NIH [R01CA187718, R01AI140442, R21AR074073, R21AI149761, T32CA115299]
- NCI Cancer Center [NCI P30 CA016520]
- Penn CFAR pilot award [P30 AI 045008]
- Penn Center for Research on Coronaviruses and Other Emerging Pathogens
The COVID-19 pandemic has posed a serious threat to global health, and research has found that activating the STING signaling pathway can effectively inhibit coronavirus infection, potentially serving as a promising target for future treatments against various strains of coronaviruses.
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.
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