Pharmacological activation of STING blocks SARS-CoV-2 infection

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

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbereabi9007
JournalScience immunology
Volume6
Issue number59
DOIs
StatePublished - May 2021
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'Pharmacological activation of STING blocks SARS-CoV-2 infection'. Together they form a unique fingerprint.

Cite this