We searched our chemical collection to identify non-N-acetylneuraminate (NeuAC) inhibitors of influenza neuraminidase (NA). Of the 62 acyl derivatives tested, several acyl amino acids, but not acyl alkanolamine derivatives, were effective and inhibited the NA activity in a dose-dependent manner. N-3-Hydroxymyristoyl D-cysteine and N-myristoyl-O-caproyl-D-serine were the more potent compounds and inhibited the enzyme in a noncompetitive manner (Ki = 102 and 125 microM, respectively) without respect to the substrate. An important consideration for the choice of inhibitor is the selectivity of the inhibition. These compounds were selective inhibitors of viral NA and effective for any variant enzyme, but the enzymes from V. cholerae and human placenta were insensitive. Accordingly, the acyl amino acid derivatives may be expected to be inhibitors without cellular toxicity and may serve as lead compounds for anti-influenza agents.