For the treatment and prophylaxis of influenza, two neuraminidase (NA) inhibitors, zanamivir (Relenza(TM)) and oseltamivir phosphate (Tamiflu(TM)), have been licensed. We have reported on laninamivir (code name, R-125489), a novel neuraminidase inhibitor, and have discovered that CS-8958, laninamivir prodrug, worked as a long acting neuraminidase inhibitor in a mouse influenza virus infection model when it was intranasally administered. In this paper, CS-8958 administered just once 7 days before infection showed significant efficacy in vivo. Then, the efficacy by a single administration of CS-8958 after viral infection was compared with that by repeated administrations of oseltamivir phosphate or zanamivir in mice and ferrets and CS-8958 showed superior or similar efficacy to the two licensed NA inhibitors. CS-8958 also significantly reduced the virus titers of an oseltamivir-resistant H1N1 virus with a neuraminidase H274Y substitution in a mouse infection model. These results suggest that, since CS-8958 is characteristically long lasting in the lungs, it may be ideal for the prophylaxis and treatment of influenza.