Portal de Periódicos da CAPES

Pharmacological activation of STING blocks SARS-CoV-2 infection

2021; American Association for the Advancement of Science; Volume: 6; Issue: 59 Linguagem: Inglês

10.1126/sciimmunol.abi9007

2470-9468

Minghua Li, Max Ferretti, Baoling Ying, Hélène C. Descamps, Emily M. Lee, Mark Dittmar, Jae Seung Lee, Kanupriya Whig, Brinda Kamalia, Lenka Dohnalová, Giulia T. Uhr, Hoda Zarkoob, Yu‐Chi Chen, Holly Ramage, Marc Ferrer, Kristen W. Lynch, D. Schultz, Christoph A. Thaiss, Michael Diamond, Sara Cherry,

Viral Infections and Outbreaks Research

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.