Innate immune pathway modulator screen identifies STING pathway activation as a strategy to inhibit multiple families of arbo and respiratory viruses.
Chikungunya virus
SARS-CoV-2
West Nile virus
Zika virus
cAIMP
cGAS-STING pathway
enterovirus-D68
pattern-recognition receptors
respiratory syncytial virus
scleroglucan
Journal
Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894
Informations de publication
Date de publication:
16 05 2023
16 05 2023
Historique:
received:
28
01
2023
revised:
17
03
2023
accepted:
07
04
2023
medline:
19
5
2023
pubmed:
30
4
2023
entrez:
29
4
2023
Statut:
ppublish
Résumé
RNA viruses continue to remain a threat for potential pandemics due to their rapid evolution. Potentiating host antiviral pathways to prevent or limit viral infections is a promising strategy. Thus, by testing a library of innate immune agonists targeting pathogen recognition receptors, we observe that Toll-like receptor 3 (TLR3), stimulator of interferon genes (STING), TLR8, and Dectin-1 ligands inhibit arboviruses, Chikungunya virus (CHIKV), West Nile virus, and Zika virus to varying degrees. STING agonists (cAIMP, diABZI, and 2',3'-cGAMP) and Dectin-1 agonist scleroglucan demonstrate the most potent, broad-spectrum antiviral function. Furthermore, STING agonists inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enterovirus-D68 (EV-D68) infection in cardiomyocytes. Transcriptome analysis reveals that cAIMP treatment rescue cells from CHIKV-induced dysregulation of cell repair, immune, and metabolic pathways. In addition, cAIMP provides protection against CHIKV in a chronic CHIKV-arthritis mouse model. Our study describes innate immune signaling circuits crucial for RNA virus replication and identifies broad-spectrum antivirals effective against multiple families of pandemic potential RNA viruses.
Identifiants
pubmed: 37119814
pii: S2666-3791(23)00134-9
doi: 10.1016/j.xcrm.2023.101024
pmc: PMC10213809
pii:
doi:
Substances chimiques
Antiviral Agents
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
101024Subventions
Organisme : NIAID NIH HHS
ID : R01 AI163216
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK132735
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY032149
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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