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Innate immune pathway modulator screen identifies STING pathway activation as a strategy to inhibit multiple families of arbo and respiratory viruses.
- Source :
-
Cell reports. Medicine [Cell Rep Med] 2023 May 16; Vol. 4 (5), pp. 101024. Date of Electronic Publication: 2023 Apr 28. - Publication Year :
- 2023
-
Abstract
- 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.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 2666-3791
- Volume :
- 4
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cell reports. Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 37119814
- Full Text :
- https://doi.org/10.1016/j.xcrm.2023.101024