Innate immune pathway modulator screen identifies STING pathway activation as a strategy to inhibit multiple families of arbo and respiratory viruses

• DOI: 10.1016/j.xcrm.2023.101024
• Publication Date: 2023-04-28T14:36:13Z
• Authors: Gustavo Garcia; Joseph Ignatius I...; Arjit Vijey Jeyac...; Swati Dubey; Christina Chang; Sebastian Castill...; Nate Price; Sathya Arumugam; Angelica L. Marquez; Aayushi Shah; Amir Fanaei; Nikhil Chakravarty; Shantanu Joshi; Sanjeev Sinha; Samuel W. French; Mark S. Parcells; Arunachalam Ramaiah; Vaithilingaraja A...
• Keywords: cGAS-STING pathway; Biomedical and clinical sciences; respiratory syncytial virus; Immunology; CHIKV; 610; Antiviral Agents; Article; Zika virus; Mice; Rare Diseases; WNV; EV-D68; pattern-recognition receptors; Biodefense; 616; Genetics; 2.1 Biological and endogenous factors; Innate; STING activator cAIMP blocks ZIKV; Animals; RNA Viruses; Biomedical and Clinical Sciences; SARS-CoV-2; Zika Virus Infection; Inflammatory and immune system; enterovirus-D68; Immunity; COVID-19; Zika Virus; Immunity, Innate; 3. Good health; Vector-Borne Diseases; Emerging Infectious Diseases; Infectious Diseases; Good Health and Well Being; Medical Microbiology; 5.1 Pharmaceuticals; antiviral activity; cAIMP; Infection; West Nile virus; Chikungunya virus; scleroglucan

RNA viruses continue to remain a threat for potential pandemics due their rapid evolution. Potentiating host antiviral pathways prevent or limit viral infections is promising strategy. Thus, by testing library of innate immune agonists targeting pathogen recognition receptors, we observe that Toll-like receptor 3 (TLR3), stimulator interferon genes (STING), TLR8, and Dectin-1 ligands inhibit arboviruses, Chikungunya virus (CHIKV), West Nile virus, Zika varying degrees. STING (cAIMP, diABZI, 2',3'-cGAMP) agonist scleroglucan demonstrate the most potent, broad-spectrum function. Furthermore, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enterovirus-D68 (EV-D68) infection in cardiomyocytes. Transcriptome analysis reveals cAIMP treatment rescue cells from CHIKV-induced dysregulation cell repair, immune, metabolic pathways. In addition, provides protection against CHIKV chronic CHIKV-arthritis mouse model. Our study describes signaling circuits crucial replication identifies antivirals effective multiple families pandemic viruses.