Diverse bat organoids provide pathophysiological models for zoonotic viruses.

Bats are important reservoirs of zoonotic pathogens, but suitable model systems for comprehensively exploring host-pathogen interactions and assessing spillover risks remain limited. To address this gap, we developed a collection of bat organoid models spanning five species and four organ types. This multispecies, multiorgan organoid panel showed species- and tissue-specific replication patterns for several viruses, offering robust pathophysiological models for studying respiratory, renal, and enteric zoonotic viruses. Using this platform, we successfully isolated and characterized bat-borne mammalian orthoreoviruses and paramyxoviruses, demonstrating the utility of these organoid panels for virome surveillance. Furthermore, we successfully tested known antiviral drugs for their efficacy against bat virus isolates.