2. Academic Validation
  3. Organotypic culture of human brain explants as a preclinical model for AI-driven antiviral studies

Organotypic culture of human brain explants as a preclinical model for AI-driven antiviral studies

  • EMBO Mol Med. 2024 Mar 12. doi: 10.1038/s44321-024-00039-9.
Emma Partiot # 1 2,  Barbara Gorda # 1 2,  Willy Lutz 1 2,  Solène Lebrun 1 2,  Pierre Khalfi 2 3,  Stéphan Mora 2 3,  Benoit Charlot 2 4,  Karim Majzoub 2 3,  Solange Desagher 1 2 3,  Gowrishankar Ganesh 2 5,  Sophie Colomb 2 6,  Raphael Gaudin 7 8
Affiliations

Affiliations

  • 1 CNRS, Institut de Recherche en Infectiologie de Montpellier (IRIM), 34293, Montpellier, France.
  • 2 Univ Montpellier, 34090, Montpellier, France.
  • 3 CNRS, Institut de Génétique Moléculaire de Montpellier (IGMM), 34293, Montpellier, France.
  • 4 Institut d'Electronique et des Systèmes IES, CNRS, 860 Rue de St - Priest Bâtiment 5, 34090, Montpellier, France.
  • 5 UM-CNRS Laboratoire d'Informatique de Robotique et de Microelectronique de Montpellier (LIRMM), 161, Rue Ada, 34090, Montpellier, France.
  • 6 Equipe de droit pénal et sciences forensiques de Montpellier (EDPFM), Univ. Montpellier, Département de médecine légale, Pôle Urgences, Centre Hospitalo-Universitaire de Montpellier, 371 Avenue du Doyen Gaston Giraud, 34285, Montpellier, France.
  • 7 CNRS, Institut de Recherche en Infectiologie de Montpellier (IRIM), 34293, Montpellier, France. raphael.gaudin@irim.cnrs.fr.
  • 8 Univ Montpellier, 34090, Montpellier, France. raphael.gaudin@irim.cnrs.fr.
  • # Contributed equally.
PMID: 38472366 DOI: 10.1038/s44321-024-00039-9
Abstract

Viral neuroinfections represent a major health burden for which the development of antivirals is needed. Antiviral compounds that target the consequences of a brain Infection (symptomatic treatment) rather than the cause (direct-acting antivirals) constitute a promising mitigation strategy that requires to be investigated in relevant models. However, physiological surrogates mimicking an adult human cortex are lacking, limiting our understanding of the mechanisms associated with viro-induced neurological disorders. Here, we optimized the Organotypic culture of Post-mortem Adult human cortical Brain explants (OPAB) as a preclinical platform for Artificial Intelligence (AI)-driven Antiviral studies. OPAB shows robust viability over weeks, well-preserved 3D cytoarchitecture, viral permissiveness, and spontaneous local field potential (LFP). Using LFP as a surrogate for neurohealth, we developed a machine learning framework to predict with high confidence the Infection status of OPAB. As a proof-of-concept, we showed that antiviral-treated OPAB could partially restore LFP-based electrical activity of infected OPAB in a donor-dependent manner. Together, we propose OPAB as a physiologically relevant and versatile model to study neuroinfections and beyond, providing a platform for preclinical drug discovery.

Keywords

Artificial Intelligence; Bunyavirus; Neurotropic Virus; Small Molecule; Tahyna Virus.

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