{"doi":"10.17615/hy4j-3r92","title":"A Chemical Strategy for Intracellular Arming of an Endogenous Broad-Spectrum Antiviral Nucleotide","abstract":"The naturally occurring nucleotide 3′-deoxy-3′,4′-didehydro-cytidine-5′-triphosphate (ddhCTP) was recently found to exert potent and broad-spectrum antiviral activity. However, nucleoside 5′-triphosphates in general are not cell-permeable, which precludes the direct use of ddhCTP as a therapeutic. To harness the therapeutic potential of this endogenous antiviral nucleotide, we synthesized phosphoramidate prodrug HLB-0532247 (1) and found it to result in dramatically elevated levels of ddhCTP in cells. We compared 1 and 3′-deoxy-3′,4′-didehydro-cytidine (ddhC) and found that 1 more effectively reduces titers of Zika and West Nile viruses in cell culture with minimal nonspecific toxicity to host cells. We conclude that 1 is a promising antiviral agent based on a novel strategy of facilitating elevated levels of the endogenous ddhCTP antiviral nucleotide.","journal":"Figshare","year":2022,"id":312442,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9585,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":106538,"name":"Anoop Narayanan","orcid":"0000-0002-6589-5285","position":1,"is_corresponding":false},{"id":1009887,"name":"Nicole M. Antczak","orcid":"0000-0001-7970-0779","position":2,"is_corresponding":false},{"id":555983,"name":"Craig E. Cameron","orcid":"0000-0002-7564-5642","position":3,"is_corresponding":false},{"id":458585,"name":"Daniel A. Harki","orcid":"0000-0001-5950-931X","position":4,"is_corresponding":false},{"id":106559,"name":"Joyce Jose","orcid":"0000-0003-1261-6921","position":5,"is_corresponding":false},{"id":337326,"name":"Jamie J. Arnold","orcid":"0000-0002-2345-9776","position":6,"is_corresponding":false},{"id":902653,"name":"Kellan T. Passow","orcid":"0009-0000-6626-7187","position":7,"is_corresponding":false},{"id":421729,"name":"Haley S. Caldwell","orcid":"0000-0002-9312-4293","position":8,"is_corresponding":false},{"id":1009888,"name":"Shana J. Sturla","orcid":"0000-0001-6808-5950","position":9,"is_corresponding":false},{"id":225802,"name":"Kiet Ngo","orcid":"0009-0002-5548-1983","position":10,"is_corresponding":false},{"id":335264,"name":"Alexander T. Ciota","orcid":"0000-0001-6589-4728","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T00:33:36.072096Z","pmid":null,"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":[]}