ArticleVirus research2021
The DHODH inhibitor PTC299 arrests SARS-CoV-2 replication and suppresses induction of inflammatory cytokines.
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Article in Virus research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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42citing papers in PubMed
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42 citing papers in PubMed, 70 citations in OpenAlex.
- Host metabolic responses to SARS-CoV-2 and influenza viruses: parallels and contrasts.Metabolomics : Official journal of the Metabolomic Society · 2026Review
- Antibody‒drug conjugates with DHODH inhibitor as novel payload class for cancer and SARS-CoV-2 infection therapies.Acta pharmaceutica Sinica. B · 2026Article
- Antimycin A inhibits alpha-herpesvirus replication by disrupting the formation of pyrimidinosomes.Journal of advanced research · 2026Article
- Quinazolinones as Bioisosteres of Naphthoquinones: A Path to PotentACS medicinal chemistry letters · 2026Article
- A deep learning drug screening framework for integrating local-global characteristics: A novel attempt for limited data.Heliyon · 2024Article
- Host factors of SARS-CoV-2 in infection, pathogenesis, and long-term effects.Frontiers in cellular and infection microbiology · 2024Review
- Cell-specific genome-scale metabolic modeling of SARS-CoV-2-infected lung to identify antiviral enzymes.FEBS open bio · 2023Article
- A Novel mechanism of herbicide action through disruption of pyrimidine biosynthesis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Multi-omics for COVID-19: driving development of therapeutics and vaccines.National science review · 2023Review
- Metabolomic analysis of pig spleen reveals African swine fever virus infection increased acylcarnitine levels to facilitate viral replication.Journal of virology · 2023Article
- A clinical pharmacokinetic drug-drug interaction study between dextromethorphan and emvododstat, a potent anti-SARS-CoV-2 dihydroorotate dehydrogenase inhibitor.European journal of clinical pharmacology · 2023Article
- Protein structure-based in-silico approaches to drug discovery: Guide to COVID-19 therapeutics.Molecular aspects of medicine · 2023Review
- A pharmacokinetic drug-drug interaction study between rosuvastatin and emvododstat, a potent anti-SARS-CoV-2 (COVID-19) DHODH (dihydroorotate dehydrogenase) inhibitor.Pharmacology research & perspectives · 2023Article
- Identification of a dihydroorotate dehydrogenase inhibitor that inhibits cancer cell growth by proteomic profiling.Oncology research · 2023Article
- Population-enriched innate immune variants may identify candidate gene targets at the intersection of cancer and cardio-metabolic disease.Frontiers in endocrinology · 2023Review
- Small molecules in the treatment of COVID-19.Signal transduction and targeted therapy · 2022Review
- Targeting Acute Myelogenous Leukemia Using Potent Human Dihydroorotate Dehydrogenase Inhibitors Based on the 2-Hydroxypyrazolo[1,5-Journal of medicinal chemistry · 2022Article
- Development of a biomarker to monitor target engagement after treatment with dihydroorotate dehydrogenase inhibitors.Biochemical pharmacology · 2022Article
- Inhibitors of Nucleotide Biosynthesis as Candidates for a Wide Spectrum of Antiviral Chemotherapy.Microorganisms · 2022Review
- SARS-CoV-2 couples evasion of inflammatory response to activated nucleotide synthesis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
Corrections and comments
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Authors and funding
23 authors at 7 institutions in 1 country.
Jeremy LubanProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, 01605, USA; Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA, 02142, USA; Massachusetts Consortium on Pathogen Readiness, Boston, MA, 02115, USA.
Rachel A SattlerDepartment of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX, 77555, USA.
Elke MühlbergerMassachusetts Consortium on Pathogen Readiness, Boston, MA, 02115, USA; Department of Microbiology, Boston University School of Medicine, Boston, MA, 02118, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, 02118, USA.
Jason D GraciPTC Therapeutics, Inc. South Plainfield, NJ, 07080, USA.
Liangxian CaoPTC Therapeutics, Inc. South Plainfield, NJ, 07080, USA.
Marla WeetallPTC Therapeutics, Inc. South Plainfield, NJ, 07080, USA.
Christopher TrottaPTC Therapeutics, Inc. South Plainfield, NJ, 07080, USA.
Joseph M ColacinoPTC Therapeutics, Inc. South Plainfield, NJ, 07080, USA.
Sina BavariUnited States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD, 21702, USA.
Caterina Strambio-De-CastilliaProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
Ellen L SuderDepartment of Microbiology, Boston University School of Medicine, Boston, MA, 02118, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, 02118, USA.
Yetao WangProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
Veronica SolovevaUnited States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD, 21702, USA.
Katherine Cintron-LuePTC Therapeutics, Inc. South Plainfield, NJ, 07080, USA.
Nikolai A NaryshkinPTC Therapeutics, Inc. South Plainfield, NJ, 07080, USA.
Mark PykettPTC Therapeutics, Inc. South Plainfield, NJ, 07080, USA.
Ellen M WelchPTC Therapeutics, Inc. South Plainfield, NJ, 07080, USA.
Kylie O'KeefePTC Therapeutics, Inc. South Plainfield, NJ, 07080, USA.
Ronald KongPTC Therapeutics, Inc. South Plainfield, NJ, 07080, USA.
Elizabeth GoodwinPTC Therapeutics, Inc. South Plainfield, NJ, 07080, USA.
Allan JacobsonDepartment of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
Slobodan PaesslerDepartment of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX, 77555, USA.
Stuart W PeltzPTC Therapeutics, Inc. South Plainfield, NJ, 07080, USA. Electronic address: speltz@ptcbio.com.
PTC Therapeutics (United States) · USUniversity of Massachusetts Chan Medical School · USThe University of Texas Medical Branch at Galveston · USUnited States Army Medical Research Institute of Infectious Diseases · USBoston University · USBroad Institute · USConcord Consortium · US
Funding
Regulatory Compliance CoreUC7AI095321 · NIAID · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Ronald O'Brien · 2014 to 2026
$159.3MProject-005UL1TR001430 · NCATS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BAIR-MERRITT, MEGAN H, CENTER, DAVID M. · 2015 to 2024
$52.3MBIOLOGY OF THE LUNG--MULTIDISCIPLINARY PROGRAMT32HL007035 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Darrell N. Kotton, JOSEPH P MIZGERD · 1985 to 2026
$24.3MThe HUSH complex in HIV-1 latencyR37AI147868 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI JEREMY LUBAN · 2019 to 2026
$6.4MInsight into the Ebola virus glycoprotein fusion mechanism gleaned from the 2013-2016 epidemic GP-A82V variantR01AI148784 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LUBAN, JEREMY · 2020 to 2024
$4.1MUTMB Clinical and Translational Science AwardTL1TR001440 · NCATS · UNIVERSITY OF TEXAS MED BR GALVESTON · PI HOMMEL, JONATHAN DEAN · 2015 to 2024
$3.4MGenetic nonsense and its consequencesR35GM122468 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI JACOBSON, ALLAN S · 2017 to 2021
$2.7MNCATS NIH HHS TL1 TR001440NHLBI NIH HHS T32 HL007035NIAID NIH HHS R01 AI148784NIAID NIH HHS R37 AI147868NIAID NIH HHS UC7 AI095321NIGMS NIH HHS R35 GM122468NIH HHS HL007035T32
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 bioavailable compound that is a potent inhibitor of dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme of the de novo pyrimidine nucleotide biosynthesis pathway. In tissue culture, PTC299 manifests robust, dose-dependent, and DHODH-dependent inhibition of SARS-COV-2 replication (EC
Indexed as
AnimalsAntiviral AgentsCarbamatesCarbazolesChlorocebus aethiopsCOVID-19 Drug TreatmentCytokine Release SyndromeCytokinesDihydroorotate DehydrogenaseHeLa CellsHumansInflammationOxidoreductases Acting on CH-CH Group DonorsSARS-CoV-2Vero CellsVirus ReplicationAntiviral AgentsCarbamatesCarbazolesCytokinesDihydroorotate DehydrogenaseemvododstatOxidoreductases Acting on CH-CH Group DonorsAntiviralCoronavirusCOVID-19CytokineCytokine stormDHODHPTC299SARS-CoV-2
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.