Pseudorabies virus (PRV) is a significant pathogen impacting swine health and poses high zoonotic risks to humans. Effective antiviral treatments for PRV remain limited, underscoring the need for novel therapeutic strategies. In this study, ciprofloxacin was identified as a repurposed promising candidate with significant in vitro inhibition of PRV replication based on our inference from PNU-183792, an HSV-1 DNA polymerase inhibitor, that quinolones have the potential to act as anti-PRV drugs. Compound A1 was firstly hopping from ciprofloxacin and PNU-183792, showing more than 500-fold higher anti-PRV activity than ciprofloxacin with an EC