In the present study, we examined the efficacy and synergy of the TCAD regimen against viruses which were resistant to oseltamivir or amantadine, including 2009 H1N1. Consistent with the previous findings [9] , we found that the 2009 H1N1 strains were susceptible to NAIs (oseltamivir carboxylate, zanamivir, and peramivir) and ribavirin, but were resistant to adamantanes (amantadine and rimantadine). Surprisingly, we found that amantadine as a single agent retained partial activity against these viruses (Table S2) , albeit the activity was reduced by 100-fold compared to a susceptible virus, whereas rimantadine had no activity below the 50% cytotoxic concentration. This observation suggests that phenotypic testing, in addition to determination of the genotype, may be necessary in order to fully understand the susceptibility profile of a novel virus and may have important implications in guiding the choice of antivirals for use in combinations.