About: The DHODH Inhibitor PTC299 Arrests SARS-CoV-2 Replication and Suppresses Induction of Inflammatory Cytokines

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About: The DHODH Inhibitor PTC299 Arrests SARS-CoV-2 Replication and Suppresses Induction of Inflammatory Cytokines Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	The DHODH Inhibitor PTC299 Arrests SARS-CoV-2 Replication and Suppresses Induction of Inflammatory Cytokines
Creator	Paessler, Slobodan Mühlberger, Elke Bavari, Sina Soloveva, Veronica Luban, Jeremy Graci, Jason Peltz, Stuart Suder, Ellen Wang, Yetao Cao, Liangxian Cintron-Lue, Katherine Colacino, Joseph Goodwin, Elizabeth Jacobson, Allan Kong, Ronald Naryshkin, Nikolai O'keefe, Kylie Pykett, Mark Sattler, Rachel Strambio-De-Castillia, Caterina Trotta, Christopher Weetall, Marla Welch, Ellen
Source	BioRxiv; Medline
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 (EC50 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.
has issue date	2020-08-05(xsd:dateTime)
bibo:doi	10.1101/2020.08.05.238394
bibo:pmid	32793904
has license	biorxiv
sha1sum (hex)	8b80eff1eafb12f076da60154892b611a007c672
schema:url	https://doi.org/10.1101/2020.08.05.238394
resource representing a document's title	The DHODH Inhibitor PTC299 Arrests SARS-CoV-2 Replication and Suppresses Induction of Inflammatory Cytokines
has PubMed identifier	32793904
schema:publication	bioRxiv
resource representing a document's body	covid:8b80eff1eafb12f076da60154892b611a007c672#body_text
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