Targeting dihydroorotate dehydrogenase (DHODH) for host-directed therapy: Discovery of a novel alkyne-based scaffold inhibitor effective against SARS-CoV-2.

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Title: Targeting dihydroorotate dehydrogenase (DHODH) for host-directed therapy: Discovery of a novel alkyne-based scaffold inhibitor effective against SARS-CoV-2.
Authors: Vaidergorn MM; Center for the Research and Advancement in Fragments and Molecular Targets (CRAFT), School of Pharmaceutical Sciences at Ribeirao Preto, University of São Paulo, Ribeirão Preto, 14040-903, SP, Brazil; Protein Crystallography Laboratory, Department of Biomolecular Sciences, School of Pharmaceutical Sciences at Ribeirao Preto, University of São Paulo, Ribeirão Preto, 14040-903, SP, Brazil; Laboratory of Heterocyclic and Medicinal Chemistry (QHeteM), Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences at Ribeirao Preto, University of São Paulo, Ribeirão Preto, 14040-903, SP, Brazil., Purificação AD; Center for the Research and Advancement in Fragments and Molecular Targets (CRAFT), School of Pharmaceutical Sciences at Ribeirao Preto, University of São Paulo, Ribeirão Preto, 14040-903, SP, Brazil; Protein Crystallography Laboratory, Department of Biomolecular Sciences, School of Pharmaceutical Sciences at Ribeirao Preto, University of São Paulo, Ribeirão Preto, 14040-903, SP, Brazil., Leite PIP; Center for the Research and Advancement in Fragments and Molecular Targets (CRAFT), School of Pharmaceutical Sciences at Ribeirao Preto, University of São Paulo, Ribeirão Preto, 14040-903, SP, Brazil; Laboratory of Heterocyclic and Medicinal Chemistry (QHeteM), Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences at Ribeirao Preto, University of São Paulo, Ribeirão Preto, 14040-903, SP, Brazil., Silva-Mendonça S; Center for the Research and Advancement in Fragments and Molecular Targets (CRAFT), School of Pharmaceutical Sciences at Ribeirao Preto, University of São Paulo, Ribeirão Preto, 14040-903, SP, Brazil; Laboratory for Molecular Modeling and Drug Design (LabMol), Faculty of Pharmacy, Universidade Federal de Goiás, Goiânia, 74605-170, GO, Brazil; Center for Excellence in Artificial Intelligence (CEIA), Institute of Informatics, Universidade Federal de Goiás, Goiânia, 74605-170, GO, Brazil., Silva WJL; Center for the Research and Advancement in Fragments and Molecular Targets (CRAFT), School of Pharmaceutical Sciences at Ribeirao Preto, University of São Paulo, Ribeirão Preto, 14040-903, SP, Brazil; Laboratory for Molecular Modeling and Drug Design (LabMol), Faculty of Pharmacy, Universidade Federal de Goiás, Goiânia, 74605-170, GO, Brazil; Center for Excellence in Artificial Intelligence (CEIA), Institute of Informatics, Universidade Federal de Goiás, Goiânia, 74605-170, GO, Brazil., Santos TD; Center for the Research and Advancement in Fragments and Molecular Targets (CRAFT), School of Pharmaceutical Sciences at Ribeirao Preto, University of São Paulo, Ribeirão Preto, 14040-903, SP, Brazil; Laboratory of Heterocyclic and Medicinal Chemistry (QHeteM), Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences at Ribeirao Preto, University of São Paulo, Ribeirão Preto, 14040-903, SP, Brazil., Silva DG; Center for the Research and Advancement in Fragments and Molecular Targets (CRAFT), School of Pharmaceutical Sciences at Ribeirao Preto, University of São Paulo, Ribeirão Preto, 14040-903, SP, Brazil; Laboratory of Heterocyclic and Medicinal Chemistry (QHeteM), Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences at Ribeirao Preto, University of São Paulo, Ribeirão Preto, 14040-903, SP, Brazil., Godoi BF; Center for the Research and Advancement in Fragments and Molecular Targets (CRAFT), School of Pharmaceutical Sciences at Ribeirao Preto, University of São Paulo, Ribeirão Preto, 14040-903, SP, Brazil; Laboratory of Heterocyclic and Medicinal Chemistry (QHeteM), Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences at Ribeirao Preto, University of São Paulo, Ribeirão Preto, 14040-903, SP, Brazil., Sacramento CQ; Laboratory of Immunopharmacology, Oswaldo Cruz Institute (IOC), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, RJ, Brazil; National Institute for Science and Technology on Innovation in Diseases of Neglected Populations (INCT/IDPN), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil., Mattos M; Laboratory of Immunopharmacology, Oswaldo Cruz Institute (IOC), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, RJ, Brazil; National Institute for Science and Technology on Innovation in Diseases of Neglected Populations (INCT/IDPN), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil., Fintelman-Rodrigues N; Laboratory of Immunopharmacology, Oswaldo Cruz Institute (IOC), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, RJ, Brazil; National Institute for Science and Technology on Innovation in Diseases of Neglected Populations (INCT/IDPN), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil., Freitas CS; Laboratory of Immunopharmacology, Oswaldo Cruz Institute (IOC), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, RJ, Brazil; National Institute for Science and Technology on Innovation in Diseases of Neglected Populations (INCT/IDPN), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil., Damasceno LEA; Center of Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, 14040-900, Brazil., Shishikura Y; Drug Discovery Unit, University of Dundee, School of Life Sciences, Dow Street, Dundee, DD1 5EH, UK., Brown A; Drug Discovery Unit, University of Dundee, School of Life Sciences, Dow Street, Dundee, DD1 5EH, UK., Wrobel K; Drug Discovery Unit, University of Dundee, School of Life Sciences, Dow Street, Dundee, DD1 5EH, UK., Riley J; Drug Discovery Unit, University of Dundee, School of Life Sciences, Dow Street, Dundee, DD1 5EH, UK., Souza TML; Laboratory of Immunopharmacology, Oswaldo Cruz Institute (IOC), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, RJ, Brazil; National Institute for Science and Technology on Innovation in Diseases of Neglected Populations (INCT/IDPN), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil., Read KD; Drug Discovery Unit, University of Dundee, School of Life Sciences, Dow Street, Dundee, DD1 5EH, UK., Alves-Filho JC; Center of Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, 14040-900, Brazil., Andrade CH; Center for the Research and Advancement in Fragments and Molecular Targets (CRAFT), School of Pharmaceutical Sciences at Ribeirao Preto, University of São Paulo, Ribeirão Preto, 14040-903, SP, Brazil; Laboratory for Molecular Modeling and Drug Design (LabMol), Faculty of Pharmacy, Universidade Federal de Goiás, Goiânia, 74605-170, GO, Brazil; Center for Excellence in Artificial Intelligence (CEIA), Institute of Informatics, Universidade Federal de Goiás, Goiânia, 74605-170, GO, Brazil. Electronic address: carolina@ufg.br., Nonato MC; Center for the Research and Advancement in Fragments and Molecular Targets (CRAFT), School of Pharmaceutical Sciences at Ribeirao Preto, University of São Paulo, Ribeirão Preto, 14040-903, SP, Brazil; Protein Crystallography Laboratory, Department of Biomolecular Sciences, School of Pharmaceutical Sciences at Ribeirao Preto, University of São Paulo, Ribeirão Preto, 14040-903, SP, Brazil. Electronic address: cristy@fcfrp.usp.br., Emery FS; Center for the Research and Advancement in Fragments and Molecular Targets (CRAFT), School of Pharmaceutical Sciences at Ribeirao Preto, University of São Paulo, Ribeirão Preto, 14040-903, SP, Brazil; Laboratory of Heterocyclic and Medicinal Chemistry (QHeteM), Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences at Ribeirao Preto, University of São Paulo, Ribeirão Preto, 14040-903, SP, Brazil. Electronic address: flavioemery@usp.br.
Source: European journal of medicinal chemistry [Eur J Med Chem] 2025 Nov 05; Vol. 297, pp. 117876. Date of Electronic Publication: 2025 Jun 21.
Publication Type: Journal Article
Journal Info: Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 0420510 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1768-3254 (Electronic) Linking ISSN: 02235234 NLM ISO Abbreviation: Eur J Med Chem Subsets: MEDLINE
Database: MEDLINE Ultimate
Description
ISSN:1768-3254
DOI:10.1016/j.ejmech.2025.117876