{"doi":"10.1101/2020.08.05.238394","title":"The DHODH Inhibitor PTC299 Arrests SARS-CoV-2 Replication and Suppresses Induction of Inflammatory Cytokines","abstract":"SUMMARY The coronavirus disease 2019 (COVID-19) pandemic has created an urgent need for therapeutics that inhibit the SARS-CoV-2 virus and suppress the fulminant inflammation characteristic of advanced illness. Here, we describe the anti-COVID-19 potential of PTC299, an orally available compound that is a potent inhibitor of dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme of the de novo pyrimidine biosynthesis pathway. In tissue culture, PTC299 manifests robust, dose-dependent, and DHODH-dependent inhibition of SARS CoV-2 replication (EC 50 range, 2.0 to 31.6 nM) with a selectivity index >3,800. PTC299 also blocked replication of other RNA viruses, including Ebola virus. Consistent with known DHODH requirements for immunomodulatory cytokine production, PTC299 inhibited the production of interleukin (IL)-6, IL-17A (also called IL-17), IL-17F, and vascular endothelial growth factor (VEGF) in tissue culture models. The combination of anti-SARS-CoV-2 activity, cytokine inhibitory activity, and previously established favorable pharmacokinetic and human safety profiles render PTC299 a promising therapeutic for COVID-19.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":121279,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9538,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":306711,"name":"Rachel A. Sattler","orcid":null,"position":1,"is_corresponding":false},{"id":232302,"name":"Elke Mühlberger","orcid":"0000-0003-3547-9376","position":2,"is_corresponding":false},{"id":305828,"name":"Jason D. Graci","orcid":"0000-0002-6329-9164","position":3,"is_corresponding":false},{"id":305829,"name":"Liangxian Cao","orcid":"0000-0002-7979-1612","position":4,"is_corresponding":false},{"id":305830,"name":"Marla Weetall","orcid":"0000-0002-2013-8096","position":5,"is_corresponding":false},{"id":305831,"name":"Christopher R. Trotta","orcid":"0000-0001-5749-0133","position":6,"is_corresponding":false},{"id":305832,"name":"Joseph M. Colacino","orcid":"0000-0002-0939-2341","position":7,"is_corresponding":false},{"id":235594,"name":"Sina Bavari","orcid":"0000-0001-8424-5635","position":8,"is_corresponding":false},{"id":305833,"name":"Caterina Strambio‐De‐Castillia","orcid":"0000-0002-1069-1816","position":9,"is_corresponding":false},{"id":232294,"name":"Ellen L. Suder","orcid":"0000-0001-9466-9204","position":10,"is_corresponding":false},{"id":284597,"name":"Yetao Wang","orcid":"0000-0001-8101-5455","position":11,"is_corresponding":false},{"id":306712,"name":"Veronica Soloveva","orcid":null,"position":12,"is_corresponding":false},{"id":305834,"name":"Katherine Cintron‐Lue","orcid":"0000-0003-4190-1609","position":13,"is_corresponding":false},{"id":305835,"name":"Nikolai A. Naryshkin","orcid":"0000-0001-6709-0758","position":14,"is_corresponding":false},{"id":306713,"name":"Mark Pykett","orcid":null,"position":15,"is_corresponding":false},{"id":306714,"name":"Ellen Welch","orcid":null,"position":16,"is_corresponding":false},{"id":306715,"name":"Kylie O’Keefe","orcid":null,"position":17,"is_corresponding":false},{"id":305836,"name":"Ronald Kong","orcid":"0000-0002-4692-7499","position":18,"is_corresponding":false},{"id":305837,"name":"Elizabeth Goodwin","orcid":"0000-0002-6218-8876","position":19,"is_corresponding":false},{"id":305838,"name":"Allan Jacobson","orcid":"0000-0002-5661-3821","position":20,"is_corresponding":false},{"id":228159,"name":"Slobodan Paessler","orcid":"0000-0002-2213-9551","position":21,"is_corresponding":false},{"id":305839,"name":"Stuart W. Peltz","orcid":"0000-0002-9158-9142","position":22,"is_corresponding":false},{"id":284590,"name":"Jeremy Luban","orcid":"0000-0001-5650-4054","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-18T23:14:42.734024Z","pmid":"32793904","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":[]}