{"doi":"10.1101/2023.01.19.524824","title":"Broad-spectrum antiviral inhibitors targeting pandemic potential RNA viruses","abstract":"RNA viruses continue to remain a clear and present threat for potential pandemics due to their rapid evolution. To mitigate their impact, we urgently require antiviral agents that can inhibit multiple families of disease-causing viruses, such as arthropod-borne and respiratory pathogens. Potentiating host antiviral pathways can prevent or limit viral infections before escalating into a major outbreak. Therefore, it is critical to identify broad-spectrum antiviral agents. We have tested a small library of innate immune agonists targeting pathogen recognition receptors, including TLRs, STING, NOD, Dectin and cytosolic DNA or RNA sensors. We observed that TLR3, STING, TLR8 and Dectin-1 ligands inhibited arboviruses, Chikungunya virus (CHIKV), West Nile virus (WNV) and Zika virus, to varying degrees. Cyclic dinucleotide (CDN) STING agonists, such as cAIMP, diABZI, and 2',3'-cGAMP, and Dectin-1 agonist scleroglucan, demonstrated the most potent, broad-spectrum antiviral function. Comparative transcriptome analysis revealed that CHIKV-infected cells had larger number of differentially expressed genes than of WNV and ZIKV. Furthermore, gene expression analysis showed that cAIMP treatment rescued cells from CHIKV-induced dysregulation of cell repair, immune, and metabolic pathways. In addition, cAIMP provided protection against CHIKV in a CHIKV-arthritis mouse model. Cardioprotective effects of synthetic STING ligands against CHIKV, WNV, SARS-CoV-2 and enterovirus D68 (EV-D68) infections were demonstrated using human cardiomyocytes. Interestingly, the direct-acting antiviral drug remdesivir, a nucleoside analogue, was not effective against CHIKV and WNV, but exhibited potent antiviral effects against SARS-CoV-2, RSV (respiratory syncytial virus), and EV-D68. Our study identifies broad-spectrum antivirals effective against multiple families of pandemic potential RNA viruses, which can be rapidly deployed to prevent or mitigate future pandemics.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":392888,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":869248,"name":"Joseph Ignatius Irudayam","orcid":null,"position":1,"is_corresponding":false},{"id":1167200,"name":"Arjit Vijay Jeyachandran","orcid":null,"position":2,"is_corresponding":false},{"id":1034302,"name":"Swati Dubey","orcid":"0000-0003-1632-7940","position":3,"is_corresponding":false},{"id":299125,"name":"Christina C. Chang","orcid":"0000-0003-0109-0725","position":4,"is_corresponding":false},{"id":869249,"name":"Sebastian Castillo Cario","orcid":null,"position":5,"is_corresponding":false},{"id":1035078,"name":"Nate Price","orcid":null,"position":6,"is_corresponding":false},{"id":1035079,"name":"Sathya Arumugam","orcid":null,"position":7,"is_corresponding":false},{"id":1035080,"name":"Angelica L. Marquez","orcid":null,"position":8,"is_corresponding":false},{"id":682813,"name":"Aayushi Shah","orcid":null,"position":9,"is_corresponding":false},{"id":1035081,"name":"Amir Fanaei","orcid":null,"position":10,"is_corresponding":false},{"id":1034303,"name":"Nikhil Chakravarty","orcid":"0000-0002-4603-1713","position":11,"is_corresponding":false},{"id":314806,"name":"Shantanu H. Joshi","orcid":"0000-0002-7292-8022","position":12,"is_corresponding":false},{"id":504428,"name":"Sanjeev Sinha","orcid":"0000-0001-8060-4231","position":13,"is_corresponding":false},{"id":319807,"name":"Samuel W. French","orcid":"0000-0002-7611-881X","position":14,"is_corresponding":false},{"id":559554,"name":"Mark S. Parcells","orcid":"0000-0003-0311-3820","position":15,"is_corresponding":false},{"id":245847,"name":"Arunachalam Ramaiah","orcid":"0000-0003-3573-6141","position":16,"is_corresponding":false},{"id":232372,"name":"Vaithilingaraja Arumugaswami","orcid":"0000-0002-6872-5118","position":17,"is_corresponding":false},{"id":232368,"name":"Gustavo Garcia","orcid":"0000-0002-1649-9251","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-19T01:19:01.355412Z","pmid":"36711787","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}