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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.
Garcia, Gustavo; Irudayam, Joseph Ignatius; Jeyachandran, Arjit Vijey; Dubey, Swati; Chang, Christina; Castillo Cario, Sebastian; Price, Nate; Arumugam, Sathya; Marquez, Angelica L; Shah, Aayushi; Fanaei, Amir; Chakravarty, Nikhil; Joshi, Shantanu; Sinha, Sanjeev; French, Samuel W; Parcells, Mark S; Ramaiah, Arunachalam; Arumugaswami, Vaithilingaraja.
  • Garcia G; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Irudayam JI; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Jeyachandran AV; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Dubey S; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Chang C; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Castillo Cario S; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Price N; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Arumugam S; Department of Mathematics, Government College Daman, Daman, Dadra and Nagar Haveli and Daman and Diu 396210, India.
  • Marquez AL; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Shah A; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Fanaei A; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Chakravarty N; Department of Epidemiology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Joshi S; Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA.
  • Sinha S; All India Institute of Medical Sciences, New Delhi, India.
  • French SW; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Parcells MS; Department of Animal and Food Sciences, Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
  • Ramaiah A; Tata Institute for Genetics and Society, Center at inStem, Bangalore 560065, India; City of Milwaukee Health Department, Milwaukee, WI 53202, USA. Electronic address: arama@milwaukee.gov.
  • Arumugaswami V; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA; California NanoSystems Institute, University of Cal
Cell Rep Med ; 4(5): 101024, 2023 05 16.
Article in English | MEDLINE | ID: covidwho-2295352
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA Viruses / Chikungunya virus / Zika Virus / Zika Virus Infection / COVID-19 Limits: Animals Language: English Journal: Cell Rep Med Year: 2023 Document Type: Article Affiliation country: J.xcrm.2023.101024

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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA Viruses / Chikungunya virus / Zika Virus / Zika Virus Infection / COVID-19 Limits: Animals Language: English Journal: Cell Rep Med Year: 2023 Document Type: Article Affiliation country: J.xcrm.2023.101024