ReviewEuropean journal of pharmacology2021
Efficacy and safety of dihydroorotate dehydrogenase (DHODH) inhibitors "leflunomide" and "teriflunomide" in Covid-19: A narrative review.
Review in European journal of pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- The Role of Pharmacogenetics in the Effectiveness of Rheumatoid Arthritis Treatment with Leflunomide.Genes · 2026Review
- Quinazolinones as Bioisosteres of Naphthoquinones: A Path to PotentACS medicinal chemistry letters · 2026Article
- Arzanol Inhibits Human Dihydroorotate Dehydrogenase and Shows Antiviral Activity.Journal of natural products · 2025Article
- ARF4-mediated intracellular transport as a broad-spectrum antiviral target.Nature microbiology · 2025Article
- Crosstalk among proximal tubular cells, macrophages, and fibroblasts in acute kidney injury: single-cell profiling from the perspective of ferroptosis.Human cell · 2024Article
- Potent Dual Polymerase/Exonuclease Inhibitory Activities of Antioxidant Aminothiadiazoles Against the COVID-19 Omicron Virus: A Promising In Silico/In Vitro Repositioning Research Study.Molecular biotechnology · 2024Article
- Unveiling the Antiviral Capabilities of Targeting Human Dihydroorotate Dehydrogenase against SARS-CoV-2.ACS omega · 2024Article
- Safety and Tolerability of KIO-101 Eye Drops in Healthy Volunteers and Patients with Ocular Surface Disease-A Phase I Study.Pharmaceutics · 2024Article
- Antirheumatic drug leflunomide attenuates atherosclerosis by regulating lipid metabolism and endothelial dysfunction via DHODH/AMPK signaling pathway.International journal of biological sciences · 2024Article
- Review
- Cloning and Characterization of YakAnimals : an open access journal from MDPI · 2023Article
- Cell-specific genome-scale metabolic modeling of SARS-CoV-2-infected lung to identify antiviral enzymes.FEBS open bio · 2023Article
- Article
- Protein structure-based in-silico approaches to drug discovery: Guide to COVID-19 therapeutics.Molecular aspects of medicine · 2023Review
- Optimization of CRISPR-Cas system for clinical cancer therapy.Bioengineering & translational medicine · 2023Review
- Article
- Strong Dual Antipolymerase/Antiexonuclease Actions of Some Aminothiadiazole Antioxidants: A PromisingAdvances in redox research · 2023Article
- Evaluation of a series of nucleoside analogs as effective anticoronaviral-2 drugs against the Omicron-B.1.1.529/BA.2 subvariant: A repurposing research study.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2023Article
- Forodesine and Riboprine Exhibit Strong Anti-SARS-CoV-2 Repurposing Potential:ACS bio & med chem Au · 2022Article
- A Series of Adenosine Analogs as the First Efficacious Anti-SARS-CoV-2 Drugs against the B.1.1.529.4 Lineage: A Preclinical Repurposing Research Study.ChemistrySelect · 2022Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dihydroorotate dehydrogenase (DHODH) is rate-limiting enzyme in biosynthesis of pyrimidone which catalyzes the oxidation of dihydro-orotate to orotate. Orotate is utilized in the biosynthesis of uridine-monophosphate. DHODH inhibitors have shown promise as antiviral agent against Cytomegalovirus, Ebola, Influenza, Epstein Barr and Picornavirus. Anti-SARS-CoV-2 action of DHODH inhibitors are also coming up. In this review, we have reviewed the safety and efficacy of approved DHODH inhibitors (leflunomide and teriflunomide) against COVID-19. In target-centered in silico studies, leflunomide showed favorable binding to active site of MPro and spike: ACE2 interface. In artificial-intelligence/machine-learning based studies, leflunomide was among the top 50 ligands targeting spike: ACE2 interaction. Leflunomide is also found to interact with differentially regulated pathways [identified by KEGG (Kyoto Encyclopedia of Genes and Genomes) and reactome pathway analysis of host transcriptome data] in cogena based drug-repurposing studies. Based on GSEA (gene set enrichment analysis), leflunomide was found to target pathways enriched in COVID-19. In vitro, both leflunomide (EC50 41.49 ± 8.8 μmol/L) and teriflunomide (EC50 26 μmol/L) showed SARS-CoV-2 inhibition. In clinical studies, leflunomide showed significant benefit in terms of decreasing the duration of viral shredding, duration of hospital stay and severity of infection. However, no advantage was seen while combining leflunomide and IFN alpha-2a among patients with prolonged post symptomatic viral shredding. Common adverse effects of leflunomide were hyperlipidemia, leucopenia, neutropenia and liver-function alteration. Leflunomide/teriflunomide may serve as an agent of importance to achieve faster virological clearance in COVID-19, however, findings needs to be validated in bigger sized placebo controlled studies.
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Registered trials
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