With the aid of flexible docking and molecular dynamics methods, an in-depth investigation is carried out on the binding mechanisms of 4-(N-acetylamino)-5-guanidino-3-(3-pentyloxy)benzoic acid (BA) with various types of neuraminidases (N1, N2 and N9 subtypes and B type). It indicates that BA is docked to the various types of neuraminidases with similar mechanisms, albeit some differences exist in the binding poses. BA matches their active sites well and forms stable complexes. The largest binding affinities with N1, N2 and N9 subtypes and B type are calculated to be －1233.62, －1385.72, －663.11 and －1058.87 kJ•mol^－1, respectively. It suggests that BA has excellent inhibiting effects to all the studied neuraminidases. The further analyses reveal that strong electrostatic and H-bonding interactions exist between BA and the conserved key active-site residues instead of the facile-mutated ones, indicating that the inhibiting effects will not be influenced obviously by mutations. Accordingly, BA is a potential anti-influenza virus drug worthy of more attention. Combined with the previous studies, we point out how to modify the BA molecule in order to enhance the inhibiting effects to the neuraminidases.

Key words: influenza, neuraminidase, benzoic-acid derivatives, molecular docking, drug design