Pharmacological activation of STING blocks SARS-CoV-2 infection
| Autor: | Holly Ramage, Christoph A. Thaiss, Minghua Li, Kristen W. Lynch, Max Ferretti, Hélène Descamps, Yu-Chi Chen, Kanupriya Whig, Hoda Zarkoob, David C. Schultz, Marc Ferrer, Emily M. Lee, Mark Dittmar, Baoling Ying, Brinda Kamalia, Sara Cherry, Lenka Dohnalová, Jae Seung Lee, Michael S. Diamond, Giulia T. Uhr |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Immunology Mice Transgenic Virus Replication Antiviral Agents Article Cell Line Mice 03 medical and health sciences 0302 clinical medicine Immunity Interferon Chlorocebus aethiops medicine Animals Humans Vero Cells Immune Evasion Innate immune system SARS-CoV-2 business.industry COVID-19 Membrane Proteins Epithelial Cells General Medicine Immunity Innate Enzyme Activation Mice Inbred C57BL Sting 030104 developmental biology Viral replication Cell culture Vero cell Benzimidazoles Interferons Signal transduction business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Sci Immunol |
| ISSN: | 2470-9468 |
| DOI: | 10.1126/sciimmunol.abi9007 |
| Popis: | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic, resulting millions of infections and deaths with few effective interventions available. Here, we demonstrate that SARS-CoV-2 evades interferon (IFN) activation in respiratory epithelial cells, resulting in a delayed response in bystander cells. Since pretreatment with IFNs can block viral infection, we reasoned that pharmacological activation of innate immune pathways could control SARS-CoV-2 infection. To identify potent antiviral innate immune agonists, we screened a panel of 75 microbial ligands that activate diverse signaling pathways and identified cyclic dinucleotides (CDNs), canonical STING agonists, as antiviral. Since CDNs have poor bioavailability, we tested the small molecule STING agonist diABZI, and found that it potently inhibits SARS-CoV-2 infection of diverse strains including variants of concern (B.1.351) by transiently stimulating IFN signaling. Importantly, diABZI restricts viral replication in primary human bronchial epithelial cells and in mice in vivo. Our study provides evidence that activation of STING may represent a promising therapeutic strategy to control SARS-CoV-2. |
| Databáze: | OpenAIRE |
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