The M2 proteins from the Danish Wisconsin-like viruses in 2005-2006 possessed the substitution S31N, associated with resistance to matrix inhibitory drugs, like amantadine [22, 44, 45, 51] . These types of drugs are not used for prophylaxis or treatment in Denmark. The S31N substitution is therefore not a local introduced resistance mutation. We cannot exclude that this substitution has arisen by chance, but it is more likely that the mutation has emerged as a resistance mutation in other countries like the USA [52] and Australia [53] where the prevalence of amantadine resistance is high. The resistance may also be related to the increased use of this drug in Asia during the SARS epidemic [21] .