PropertyValue
?:abstract
  • 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-17 F, 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.
is ?:annotates of
?:creator
?:doi
?:doi
  • 10.1016/j.virusres.2020.198246
?:journal
  • Virus_Res
?:license
  • no-cc
?:pdf_json_files
  • document_parses/pdf_json/a6816b36e6d251e21e3f15cd2d83e2072a6900df.json
?:pmc_json_files
  • document_parses/pmc_json/PMC7690341.xml.json
?:pmcid
?:pmid
?:pmid
  • 33249060.0
?:publication_isRelatedTo_Disease
is ?:relation_isRelatedTo_publication of
?:sha_id
?:source
  • Elsevier; Medline; PMC
?:title
  • The DHODH Inhibitor PTC299 Arrests SARS-CoV-2 Replication and Suppresses Induction of Inflammatory Cytokines
?:type
?:year
  • 2020-11-26

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