Carnosol inhibits influenza A virus by disrupting the viral envelope and interfering with Jak2/STAT3 signaling pathway

Carnosol is a natural diterpenoid compound derived from rosemary, a traditional Chinese herbal medicine used to treat many diseases. Recent studies have shown that carnosol has many pharmacological activities, including antioxidant, anti-inflammatory, and anticancer effects. In this study, the inhibitory activity and mechanism of action of carnosol against the influenza A virus (IAV) were investigated both in vitro and in vivo. Plaque and immunofluorescence assays were performed to evaluate the anti-IAV effects of carnosol in vitro. The antiviral mechanism was investigated using hemagglutination inhibition (HI) assay, virucidal assay, electron microscopy, and western blotting. anti-IAV activity in vivo was determined using a mouse pneumonia model combined with HE staining. The results showed that carnosol significantly inhibited H1N1 virus propagation in vitro and may block IAV infection by inactivating viral particles and interfering with some early stages of virus adsorption. The cellular Jak2/STAT3 signaling pathway may be involved in the anti-IAV effects of carnosol. Importantly, oral administration of carnosol significantly improved survival and reduced the symptoms of pneumonia in IAV-infected mice, comparable to the effect of oseltamivir. Thus, the natural compound carnosol has the potential to be developed as a novel anti-IAV agent.