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

Abstract

(Figure presented.) Studying the impact of viral infections of the human brain requires models reflecting the physiological complexity of neural structures and circuitries. Hence, the development of innovative strategies coupled to advanced analytic tools is needed to allow robust preclinical antiviral assessments. Organotypic culture of Post-mortem Adult human cortical Brain explants (OPAB) was established for up to 60 days. OPAB retained major neural cell types, spontaneous electrical activity and good overall viability Human neurons and OPAB were permissive to Tahyna virus (bunyavirus), and the novel proprietary small molecule RG10b exhibited significant antiviral potency in these models. AI-driven prediction based on the local field potential of OPAB highlighted that, despite good inhibition of viral replication, RG10b only partially restored “neurohealth”, in a donor-dependent manner. A physiologically-relevant AI-based platform has been established for assessing antiviral potency in preclinical, animal-free, settings.