Pharmacological activation of STING blocks SARS-CoV-2 infection.
Animals
Antiviral Agents
/ pharmacology
Benzimidazoles
/ pharmacology
COVID-19
/ prevention & control
Cell Line
Chlorocebus aethiops
Enzyme Activation
/ drug effects
Epithelial Cells
/ virology
Humans
Immune Evasion
/ immunology
Immunity, Innate
/ drug effects
Interferons
/ immunology
Membrane Proteins
/ agonists
Mice
Mice, Inbred C57BL
Mice, Transgenic
SARS-CoV-2
/ growth & development
Vero Cells
Virus Replication
/ drug effects
Journal
Science immunology
ISSN: 2470-9468
Titre abrégé: Sci Immunol
Pays: United States
ID NLM: 101688624
Informations de publication
Date de publication:
18 05 2021
18 05 2021
Historique:
received:
07
04
2021
accepted:
13
05
2021
entrez:
19
5
2021
pubmed:
20
5
2021
medline:
2
6
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34010142
pii: 6/59/eabi9007
doi: 10.1126/sciimmunol.abi9007
pmc: PMC10021026
mid: NIHMS1879523
pii:
doi:
Substances chimiques
Antiviral Agents
0
Benzimidazoles
0
Membrane Proteins
0
STING1 protein, human
0
Interferons
9008-11-1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI074951
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI140539
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI151882
Pays : United States
Organisme : NIH HHS
ID : 1R21AI140539
Pays : United States
Organisme : Intramural NIH HHS
ID : TR000414-01
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI055400
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI122749
Pays : United States
Informations de copyright
Copyright © 2021, American Association for the Advancement of Science.
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