A Broad Antiviral Strategy: Inhibitors of Human DHODH Pave the Way for Host-Targeting Antivirals against Emerging and Re-Emerging Viruses

Pyrimidine inhibitors synergize with nucleoside analogues to block SARS-CoV-2

(2022) David C. Schultz et al.   NATURE

The immunology and immunopathology of COVID-19

(2022) Miriam Merad et al.   SCIENCE

Effective deploying of a novel DHODH inhibitor against herpes simplex type 1 and type 2 replication

(2021) Anna Luganini et al.   ANTIVIRAL RESEARCH

Leflunomide an immunomodulator with antineoplastic and antiviral potentials but drug-induced liver injury: A comprehensive review

(2021) Raghad D. Alamri et al.   INTERNATIONAL IMMUNOPHARMACOLOGY

DHODH and cancer: promising prospects to be explored

(2021) Yue Zhou et al.   Cancer & Metabolism

Inhibiting pyrimidine biosynthesis impairs Peste des Petits Ruminants Virus replication through depletion of nucleoside pools and activation of cellular immunity

(2021) Li Jin et al.   VETERINARY MICROBIOLOGY

A Bioluminescent 3CLPro Activity Assay to Monitor SARS-CoV-2 Replication and Identify Inhibitors

(2021) Cyrille Mathieu et al.   Viruses-Basel

The New Generation hDHODH Inhibitor MEDS433 Hinders the In Vitro Replication of SARS-CoV-2 and Other Human Coronaviruses

(2021) Arianna Calistri et al.   Microorganisms

Novel quinolone derivatives targeting human dihydroorotate dehydrogenase suppress Ebola virus infection in vitro

(2021) Mingli Gong et al.   ANTIVIRAL RESEARCH

Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro

(2020) Manli Wang et al.   CELL RESEARCH

The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus

(2020) Calvin J Gordon et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Compassionate Use of Remdesivir for Patients with Severe Covid-19

(2020) Jonathan Grein et al.   NEW ENGLAND JOURNAL OF MEDICINE

Structure of the RNA-dependent RNA polymerase from COVID-19 virus

(2020) Yan Gao et al.   SCIENCE

A77 1726, the active metabolite of the anti‐rheumatoid arthritis drug leflunomide, inhibits influenza A virus replication in vitro and in vivo by inhibiting the activity of Janus kinases

(2020) Jiongjiong Wang et al.   FASEB JOURNAL

Targeting virus–host interaction by novel pyrimidine derivative: an in silico approach towards discovery of potential drug against COVID-19

(2020) Jitendra Subhash Rane et al.   JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS

Cytokine storm and leukocyte changes in mild versus severe SARS‐CoV‐2 infection: Review of 3939 COVID‐19 patients in China and emerging pathogenesis and therapy concepts

(2020) Jin Wang et al.   JOURNAL OF LEUKOCYTE BIOLOGY

Potential treatment of COVID-19 by inhibitors of human dihydroorotate dehydrogenase

(2020) Yechun Xu et al.   Protein & Cell

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

(2020) Rui Xiong et al.   Protein & Cell

Vidofludimus calcium, a next generation DHODH inhibitor for the Treatment of relapsing-remitting multiple sclerosis

(2020) Andreas Muehler et al.   Multiple Sclerosis and Related Disorders

A Small-Scale Medication of Leflunomide as a Treatment of COVID-19 in an Open-Label Blank-Controlled Clinical Trial

(2020) Ke Hu et al.   VIROLOGICA SINICA

Current knowledge about the antivirals remdesivir (GS-5734) and GS-441524 as therapeutic options for coronaviruses

(2020) E. Susan Amirian et al.   One Health

Immunopathology of Hyperinflammation in COVID-19

(2020) Joshua N. Gustine et al.   AMERICAN JOURNAL OF PATHOLOGY

Cytokine storm induced by SARS-CoV-2

(2020) Peipei Song et al.   CLINICA CHIMICA ACTA

The enzymatic activity of the nsp14 exoribonuclease is critical for replication of MERS-CoV and SARS-CoV-2

(2020) Natacha S. Ogando et al.   JOURNAL OF VIROLOGY

Identification of Inhibitors of ZIKV Replication

(2020) Desarey Morales Vasquez et al.   Viruses-Basel

Recommendations for treatment of critically ill patients with COVID-19

(2020) S. Kluge et al.   ANAESTHESIST

The place for remdesivir in COVID-19 treatment

(2020) Barnaby Young et al.   LANCET INFECTIOUS DISEASES

The DHODH inhibitor PTC299 arrests SARS-CoV-2 replication and suppresses induction of inflammatory cytokines

(2020) Jeremy Luban et al.   VIRUS RESEARCH

IMU-838, a Developmental DHODH Inhibitor in Phase II for Autoimmune Disease, Shows Anti-SARS-CoV-2 and Broad-Spectrum Antiviral Efficacy In Vitro

(2020) Friedrich Hahn et al.   Viruses-Basel

Influenza infection, SARS, MERS and COVID-19: Cytokine storm – The common denominator and the lessons to be learned

(2020) Varvara A. Ryabkova et al.   CLINICAL IMMUNOLOGY

Reversible alopecia areata: a little known side effect of leflunomide

(2019) Greg Koller et al.   CLINICAL RHEUMATOLOGY

Discovery, Optimization, and Target Identification of Novel Potent Broad-Spectrum Antiviral Inhibitors

(2019) Yiqing Yang et al.   JOURNAL OF MEDICINAL CHEMISTRY

The novel dihydroorotate dehydrogenase (DHODH) inhibitor BAY 2402234 triggers differentiation and is effective in the treatment of myeloid malignancies

(2019) Sven Christian et al.   LEUKEMIA

Broad-Spectrum Antiviral Agents: A Crucial Pandemic Tool

(2019) Amesh Adalja et al.   Expert Review of Anti-Infective Therapy

Antiviral activity of brequinar against foot-and-mouth disease virus infection in vitro and in vivo

(2019) Shi-fang Li et al.   BIOMEDICINE & PHARMACOTHERAPY

Antiviral effects of selected IMPDH and DHODH inhibitors against foot and mouth disease virus

(2019) Gong Mei-jiao et al.   BIOMEDICINE & PHARMACOTHERAPY

Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine

(2019) Andersen et al.   Viruses-Basel

From “A”IV to “Z”IKV: Attacks from Emerging and Re-emerging Pathogens

(2018) George F. Gao   CELL

Antiviral activity of A771726, the active metabolite of leflunomide, against Junín virus

(2018) Claudia S. Sepúlveda et al.   JOURNAL OF MEDICAL VIROLOGY

Targeting Myeloid Differentiation Using Potent 2-Hydroxypyrazolo[1,5-a]pyridine Scaffold-Based Human Dihydroorotate Dehydrogenase Inhibitors

(2018) Stefano Sainas et al.   JOURNAL OF MEDICINAL CHEMISTRY

Inhibiting pyrimidine biosynthesis impairs Ebola virus replication through depletion of nucleoside pools and activation of innate immune responses

(2018) Priya Luthra et al.   ANTIVIRAL RESEARCH

Targeting of Hematologic Malignancies with PTC299, A Novel Potent Inhibitor of Dihydroorotate Dehydrogenase with Favorable Pharmaceutical Properties

(2018) Liangxian Cao et al.   MOLECULAR CANCER THERAPEUTICS

Dihydroorotate dehydrogenase: A drug target for the development of antimalarials

(2017) Anju Singh et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Broad-spectrum inhibition of common respiratory RNA viruses by a pyrimidine synthesis inhibitor with involvement of the host antiviral response

(2017) Nam Nam Cheung et al.   JOURNAL OF GENERAL VIROLOGY

Chikungunya virus: an update on the biology and pathogenesis of this emerging pathogen

(2017) Felicity J Burt et al.   LANCET INFECTIOUS DISEASES

Leflunomide/teriflunomide inhibit Epstein-Barr virus (EBV)-induced lymphoproliferative disease and lytic viral replication

(2017) Andrea Bilger et al.   Oncotarget

Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice

(2016) Rudragouda Channappanavar et al.   Cell Host & Microbe

Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys

(2016) Travis K. Warren et al.   NATURE

Disease-Promoting Effects of Type I Interferons in Viral, Bacterial, and Coinfections

(2015) Sophia Davidson et al.   JOURNAL OF INTERFERON AND CYTOKINE RESEARCH

Design, Synthesis, X-ray Crystallographic Analysis, and Biological Evaluation of Thiazole Derivatives as Potent and Selective Inhibitors of Human Dihydroorotate Dehydrogenase

(2015) Junsheng Zhu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Dengue

(2015) Maria G Guzman et al.   LANCET

Rational Design of Benzylidenehydrazinyl-Substituted Thiazole Derivatives as Potent Inhibitors of Human Dihydroorotate Dehydrogenase with in Vivo Anti-arthritic Activity

(2015) Shiliang Li et al.   Scientific Reports

Leflunomide and teriflunomide: altering the metabolism of pyrimidines for the treatment of autoimmune diseases

(2015) Yara Dadalti Fragoso et al.   Expert Review of Clinical Pharmacology

On Dihydroorotate Dehydrogenases and Their Inhibitors and Uses

(2013) Hélène Munier-Lehmann et al.   JOURNAL OF MEDICINAL CHEMISTRY

Inhibition of Arenavirus by A3, a Pyrimidine Biosynthesis Inhibitor

(2013) E. Ortiz-Riano et al.   JOURNAL OF VIROLOGY

Inhibition of Pyrimidine Biosynthesis Pathway Suppresses Viral Growth through Innate Immunity

(2013) Marianne Lucas-Hourani et al.   PLoS Pathogens

Broad-spectrum antiviral that interferes with de novo pyrimidine biosynthesis

(2011) H.-H. Hoffmann et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Leflunomide for cytomegalovirus: bench to bedside

(2011) B. Chacko et al.   Transplant Infectious Disease

Characterization of Dengue Virus Resistance to Brequinar in Cell Culture

(2010) M. Qing et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Exacerbated Innate Host Response to SARS-CoV in Aged Non-Human Primates

(2010) Saskia L. Smits et al.   PLoS Pathogens

Leflunomide Inhibition of BK Virus Replication in Renal Tubular Epithelial Cells

(2009) E. Bernhoff et al.   JOURNAL OF VIROLOGY

Early Upregulation of Acute Respiratory Distress Syndrome-Associated Cytokines Promotes Lethal Disease in an Aged-Mouse Model of Severe Acute Respiratory Syndrome Coronavirus Infection

(2009) B. Rockx et al.   JOURNAL OF VIROLOGY