The results from this comprehensive analysis of group 2 p57N2, atypical group 1 p09N1 and typical group 1 N5 support the hypothesis that influenza NA inhibitors which more closely resemble the NA transition state analogue, Neu5Ac2en, are more likely to remain effective against NAs from both groups and with various drug-resistant amino acid substitutions. The gene discussed is XK; the disease is influenza.