• Nanchangmycin exhibits potent antiviral activity against influenza A virus (IAV) in vitro and in vivo, with sub-micromolar efficacy against oseltamivir-resistant strains.
• The compound shows broad-spectrum antiviral effects against multiple viruses, including pseudorabies virus, herpes virus, porcine epidemic diarrhea virus, and porcine reproductive and respiratory syndrome virus.
• Mechanistically, nanchangmycin blocks endosomal acidification, thereby inhibiting the nuclear migration of viral nucleoproteins (NPs) and trapping them in perinuclear endosomes.
• These findings position nanchangmycin as a promising candidate for developing novel anti-influenza therapeutics, especially against drug-resistant IAV strains.