2. Academic Validation
  3. Human liver-derived organoids recapitulate Oropouche virus infection and manifestation, enabling antiviral drug discovery

Human liver-derived organoids recapitulate Oropouche virus infection and manifestation, enabling antiviral drug discovery

  • Cell Rep Med. 2026 Mar 17;7(3):102646. doi: 10.1016/j.xcrm.2026.102646.
Jiajing Li 1,  Xin Wang 1,  Yibo Ding 2,  Fang Qin 2,  Shirlene T S de Lima 3,  Lito Papamichail 4,  Rick Schraauwen 5,  Julia Forato 6,  Ingra M Claro 7,  Xinyi Hua 7,  Leda M Simões Mello 8,  Dewy Mae Offermans 1,  Monique M A Verstegen 9,  Marjan Boter 10,  Maikel P Peppelenbosch 1,  Anna Barbiero 11,  Elisabetta Pagani 12,  Harry L A Janssen 13,  José A Telmos Silva 14,  Magnun N N Dos Santos 15,  Eder C Pincinato 15,  José Luiz Proenca-Modena 6,  Pengfei Li 1,  Adam A Anas 16,  Luc J W van der Laan 9,  Concetta Castilletti 17,  Bas B Oude Munnink 10,  William M de Souza 18,  Wenshi Wang 19,  Qiuwei Pan 20
Affiliations

Affiliations

  • 1 Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands.
  • 2 Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou 221004, China.
  • 3 Department of Microbiology, Immunology, and Molecular Genetics, College of Medicine, University of Kentucky, Lexington, KY, USA; Laboratório Central de Saúde Pública do Ceará, Fortaleza, Brazil; Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.
  • 4 Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.
  • 5 Department of Pathology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands.
  • 6 Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.
  • 7 Department of Microbiology, Immunology, and Molecular Genetics, College of Medicine, University of Kentucky, Lexington, KY, USA.
  • 8 Laboratório Central de Saúde Pública do Ceará, Fortaleza, Brazil.
  • 9 Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.
  • 10 Department of Viroscience, Erasmus MC-University Medical Center, Rotterdam, the Netherlands.
  • 11 Experimental and Clinical Medicine Department, University of Florence, Florence, Italy.
  • 12 Laboratory of Microbiology and Virology, Provincial Hospital of Bolzano (SABES-ASDAA), Lehrkrankenhaus der Paracelsus Medizinischen Privatuniversität, Bolzano, Italy.
  • 13 Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands; Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, ON, Canada.
  • 14 Laboratório do Hospital da Mulher de Fortaleza, Fortaleza, Brazil.
  • 15 Department of Clinical Pathology, School of Medical Sciences, University of Campinas, Campinas, Brazil.
  • 16 Department of Medical Microbiology and Infectious Diseases, Erasmus MC-University Medical Center, Rotterdam, the Netherlands; Department of Internal Medicine, Section of Infectious Diseases, Erasmus MC-University Medical Center, Rotterdam, the Netherlands.
  • 17 Department of Infectious-Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, 37024 Verona, Italy.
  • 18 Department of Microbiology, Immunology, and Molecular Genetics, College of Medicine, University of Kentucky, Lexington, KY, USA. Electronic address: [email protected].
  • 19 Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou 221004, China. Electronic address: [email protected].
  • 20 Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands. Electronic address: [email protected].
PMID: 41806841 DOI: 10.1016/j.xcrm.2026.102646
Abstract

Oropouche virus (OROV) is a neglected, re-emerging arbovirus that typically causes self-limiting febrile illness but can also lead to severe complications. With no approved vaccines or treatments available, we integrate clinical data with human liver-derived organoids to assess liver involvement in OROV Infection and identify Antiviral candidates through drug repurposing. Patient blood tests show elevated liver Enzymes, indicating OROV-associated hepatic dysfunction. OROV isolates productively infect liver organoids and induce severe cellular damage. Transcriptomic profiling reveals strong virus-host interactions, including activation of interferon-stimulated genes and cell death pathways. Pharmacological inhibition of the interferon pathway enhances OROV replication, whereas treatment with therapeutic interferon-α suppresses the Infection. Molnupiravir, a clinically approved Antiviral drug targeting viral RNA-dependent RNA polymerase, markedly inhibits OROV replication and mitigates virus-induced cytopathology. Combining molnupiravir with interferon-α results in synergistic Antiviral activity, indicating the complementarity of virus-targeted and host-directed strategies. These findings strengthen preparedness and response to OROV emergence.

Keywords

Oropouche emergence; liver; organoids; therapeutic discovery.

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